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Hier finden Sie alle Referenzen, welche im Buch in dem jeweiligen Kapitel zitiert wurden.

Kapitel 1

E. Schrödinger (1999): Was ist Leben?
Type: book by Piper Verlag {GmbH}.

E. Sackmann (1996): Supported membranes: scientific and practical applications
Type: article by Science {(New} York, {N.Y.)}.
link: http://www.ncbi.nlm.nih.gov/pubmed/8539599
Abstract:

Scientific and practical applications of supported lipid-protein bilayers are described. Membranes can be covalently coupled to or separated from solids by ultrathin layers of water or soft polymer cushions. The latter systems maintain the structural and dynamic properties of free bilayers, forming a class of models of biomembranes that allow the application of a manifold of surface-sensitive techniques. They form versatile models of low-dimensionality complex fluids, which can be used to study interfacial forces and wetting phenomena, and enable the design of phantom cells to explore the interplay of lock-and-key forces (such as receptor-ligand binding) and universal forces for cell adhesion. Practical applications are the design of (highly selective) receptor surfaces of biosensors on electrooptical devices or the biofunctionalization of inorganic solids.

E. Mayr (2002): Die Entwicklung der biologischen Gedankenwelt: Vielfalt, Evolution und Vererbung
Type: book by Springer, Berlin.

E. Mach (1963): Die Mechanik
Type: book by Wissenschaftl. Buchgesellschaft.

P. M. Kulesa, S. E. Fraser (2002): Cell dynamics during somite boundary formation revealed by time-lapse analysis
Type: article by Science {(New} York, {N.Y.)}.
doi: 10.1126/science.1075544
link: http://www.ncbi.nlm.nih.gov/pubmed/12411697
Abstract:

We follow somite segmentation in living chick embryos and find that the shaping process is not a simple periodic slicing of tissue blocks but a much more carefully choreographed separation in which the somite pulls apart from the segmental plate. Cells move across the presumptive somite boundary and violate gene expression boundaries thought to correlate with the site of the somite boundary. Similarly, cells do not appear to be preassigned to a given somite as they leave the node. The results offer a detailed picture of somite shaping and provide a spatiotemporal framework for linking gene expression with cell movements.

J. Keckes, I. Burgert, K. Frühmann, M. Müller, K. Kölln, M. Hamilton, M. Burghammer, S. V. Roth, S. Stanzl-Tschegg, P. Fratzl (2003): Cell-wall recovery after irreversible deformation of wood
Type: article by Nature Materials.
doi: 10.1038/nmat1019
link: http://www.ncbi.nlm.nih.gov/pubmed/14625541
Abstract:

The remarkable mechanical properties of biological materials reside in their complex hierarchical architecture and in specific molecular mechanistic phenomena. The fundamental importance of molecular interactions and bond recovery has been suggested by studies on deformation and fracture of bone and nacre. Like these mineral-based materials, wood also represents a complex nanocomposite with excellent mechanical performance, despite the fact that it is mainly based on polymers. In wood, however, the mechanistic contribution of processes in the cell wall is not fully understood. Here we have combined tensile tests on individual wood cells and on wood foils with simultaneous synchrotron X-ray diffraction analysis in order to separate deformation mechanisms inside the cell wall from those mediated by cell-cell interactions. We show that tensile deformation beyond the yield point does not deteriorate the stiffness of either individual cells or foils. This indicates that there is a dominant recovery mechanism that re-forms the amorphous matrix between the cellulose microfibrils within the cell wall, maintaining its mechanical properties. This stick-slip mechanism, rather like Velcro operating at the nanometre level, provides a 'plastic response' similar to that effected by moving dislocations in metals. We suggest that the molecular recovery mechanism in the cell matrix is a universal phenomenon dominating the tensile deformation of different wood tissue types.

J. L. van Hemmen (2001): Die Karte im Kopf - Wie stellt das Gehirn seine Umwelt dar?
Type: article by Physikalische Blätter.

H. von Helmholtz, A. Wangerin (2009): Über die Erhaltung der Kraft
Type: book by Deutsch {(Harri)}.

M. Fritz, A. Belcher, M. Radmacher, D. Walters, P. Hansma, G. Stucky, D. Morse, S. Mann (1994): Flat pearls from biofabrication of organized composites on inorganic substrates
Type: article by Nature.
link: http://dx.doi.org/10.1038/371049a0

P. Fratzl (2002): Von Knochen, Holz und Zähnen
Type: article by Physik Journal.
Abstract:

Biologische Materialien wie Holz, Knochen

oder Zähne sind im Laufe der Evolution von der Natur für ihre jeweilige Anwendung optimiert worden. Die Bauprinzipien dieser Gewebe, ihre Eigenschaften und ihre Funktion liefern für die Materialwissenschaft wichtige Erkenntnisse, die sich für „biomimetisches“ Design von neuartigen Werkstoffen einsetzen lassen. Anstatt viele (teure) Grundstoffe zu verwenden, kommt die Natur für den Großteil ihrer Materialien mit relativ wenigen Grundelementen aus, die gezielt strukturiert werden. Die meisten dieser Prinzipien sind noch unbekannt oder physikalisch unverstanden und bieten ein noch kaum erkundetes Betätigungsfeld für den Materialphysiker. Mögliche Anwendungen liegen in der Entwicklung von Werkstoffen für die Biomedizin (z. B. Knochenersatzmaterialien), aber auch für neuartige Sensoren oder intelligente Materialien.

E. Arzt, S. Gorb, R. Spolenak (2003): From micro to nano contacts in biological attachment devices
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
doi: 10.1073/pnas.1534701100
link: http://www.ncbi.nlm.nih.gov/pubmed/12960386
Abstract:

Animals with widely varying body weight, such as flies, spiders, and geckos, can adhere to and move along vertical walls and even ceilings. This ability is caused by very efficient attachment mechanisms in which patterned surface structures interact with the profile of the substrate. An extensive microscopic study has shown a strong inverse scaling effect in these attachment devices. Whereas microm dimensions of the terminal elements of the setae are sufficient for flies and beetles, geckos must resort to sub-microm devices to ensure adhesion. This general trend is quantitatively explained by applying the principles of contact mechanics, according to which splitting up the contact into finer subcontacts increases adhesion. This principle is widely spread in design of natural adhesive systems and may also be transferred into practical applications.

L. Addadi, D. Joester, F. Nudelman, S. Weiner (2006): Mollusk shell formation: a source of new concepts for understanding biomineralization processes.
Type: article by Chemistry {(Weinheim} an der Bergstrasse, Germany).
link: http://dx.doi.org/10.1002/chem.200500980
Abstract:

The biological approach to forming crystals is proving to be most surprising. Mollusks build their shells by using a hydrophobic silk gel, very acidic aspartic acid rich proteins, and apparently also an amorphous precursor phase from which the crystals form. All this takes place in a highly structured chitinous framework. Here we present ideas on how these disparate components work together to produce the highly structured pearly nacreous layer of the mollusk shell.

Kapitel 2

T. D. Pollard, W. C. Earnshaw, J. Lippincott-Schwartz (2007): Cell Biology
Type: book by Saunders.

L. Margulis, K. V. Schwartz (1989): Die fünf Reiche der Organismen. Ein Leitfaden
Type: book by Heidelberg : Spektrum der Wissenschaft.

H. Lodish, A. Berk, C. A. Kaiser, M. Krieger, M. P. Scott, A. Bretscher (2007): Molecular Cell Biology
Type: book by Palgrave Macmillan.

R. Lipowsky, E. Sackmann (1996): Architecture and Function. Handbook of Biological Physics Vol I
Type: book by Elsevier.
Abstract:

The first volume of the Handbook deals with the amazing world of biomembranes and lipid bilayers. Part A describes all aspects related to the morphology of these membranes, beginning with the complex architecture of biomembranes, continues with a description of the bizarre morphology of lipid bilayers and concludes with technological applications of these membranes. The first two chapters deal with biomembranes, providing an introduction to the membranes of eucaryotes and a description of the evolution of membranes. The following chapters are concerned with different aspects of lipids including the physical properties of model membranes composed of lipid-protein mixtures, lateral phase separation of lipids and proteins and measurement of lipid-protein bilayer diffusion. Other chapters deal with the flexibility of fluid bilayers, the closure of bilayers into vesicles which attain a large variety of different shapes, and applications of lipid vesicles and liposomes.

Part B covers membrane adhesion, membrane fusion and the interaction of biomembranes with polymer networks such as the cytoskeleton. The first two chapters of this part discuss the generic interactions of membranes from the conceptual point of view. The following two chapters summarize the experimental work on two different bilayer systems. The next chapter deals with the process of contact formation, focal bounding and macroscopic contacts between cells. The cytoskeleton within eucaryotic cells consists of a network of relatively stiff filaments of which three different types of filaments have been identified. As explained in the next chapter much has been recently learned about the interaction of these filaments with the cell membrane. The final two chapters deal with membrane fusion.

S. F. Gilbert, S. R. Singer (2006): Developmental Biology
Type: book by Palgrave Macmillan.

W. Fritsche (2001): Mikrobiologie
Type: book by Spektrum Akademischer Verlag.

J. M. Berg, L. Stryer, J. L. Tymoczko (2007): Biochemie
Type: book by Spektrum Akademischer Verlag.

B. Alberts, A. Johnson, P. Walter, J. Lewis, M. Raff, K. Roberts (2008): Molecular Biology of the Cell
Type: book by Taylor & Francis.

Kapitel 3

I. Tinoco, K. Sauer (2003): Physical Chemistry: Principles and Applications in Biological Sciences
Type: book by Pearson Education {(US)}.

G. Thews, E. Mutschler, P. Vaupel (2007): Anatomie, Physiologie, Pathophysiologie des Menschen
Type: book by Wissenschaftliche Verlagsgesellschaft.

F. Reif, W. Muschik (1987): Statistische Physik und Theorie der Wärme
Type: book by Gruyter.

D. J. Randall, W. Burggren, K. French (2001): Eckert Animal Physiology
Type: book by Palgrave Macmillan.

L. D. Landau, E. M. Lifschitz (1987): Lehrbuch der theoretischen Physik, 10 Bde., Bd.5, Statistische Physik: {BD} 5
Type: book by Deutsch {(Harri)}.

T. L. Hill (1988): An Introduction to Statistical Thermodynamics
Type: book by Dover Pubn Inc..

K. A. Dill, S. Bromberg (2002): Molecular driving forces: statistical thermodynamics in chemistry and biology
Type: book by Garland Pub.

R. Cahn, W. Ludwig (1985): Theorie der Wärme.
Type: book by Springer, Berlin.

G. B. Benedek, F. M. H. Villars (2000): Physics With Illustrative Examples From Medicine and Biology: Volume 2: Statistical Physics
Type: book by Springer, Berlin.

Kapitel 4

G. Wedler (2004): Lehrbuch der Physikalischen Chemie: Funfte, Vollstandig Uberarbeitete Und Aktualisierte Auflage
Type: book by {Wiley-VCH}.

I. Tinoco, K. Sauer (2003): Physical Chemistry: Principles and Applications in Biological Sciences
Type: book by Pearson Education {(US)}.

U. Schindewolf (1968): Formation and Properties of Solvated Electrons
Type: article by Angewandte Chemie International Edition in English.
doi: 10.1002/anie.196801901
link: http://dx.doi.org/10.1002/anie.196801901
Abstract:

In the formulation of many chemical reactions, electrons are regarded as readily transferable particles, though their participation in these reactions cannot be directly observed. However, the discovery that electrons can be produced in various ways in suitable solutions and that they are stabilized by solvation and can thus be studied directly has recently led to a rapid growth of interest in these, the simplest and most reactive particles of chemistry. The solvated electron has physical properties that permit its detection by various methods even at very low concentrations, so that it is also possible to follow its many reactions, most of which are extremely fast.

D. Marx, M. E. Tuckerman, J. Hutter, M. Parrinello (1999): The nature of the hydrated excess proton in water
Type: article by Nature.
doi: 10.1038/17579
link: http://dx.doi.org/10.1038/17579

I. N. Levine (2009): Physical Chemistry
Type: book by {Mcgraw-Hill} {Publ.Comp.}.

G. Kortüm, W. Vogel (1970): Lehrbuch der Elektrochemie
Type: book by Verl. Chemie.

F. Kohlrausch, A. Heydweiller (1894): Über reines Wasser
Type: article by Annalen der Physik.
link: http://adsabs.harvard.edu/abs/1894AnP...289..209K

P. Karlson, D. Doenecke, J. Koolman, G. Fuchs, W. Gerok (2005): Karlsons Biochemie und Pathobiochemie
Type: book by Thieme, Stuttgart.

M. Eigen (1964): Proton transfer, acid-base catalysis, and enzymatic hydrolysis. Part I: elementary processes
Type: article by Angewandte Chemie International Edition in English.

J. O'M Bockris, A. K. N. Reddy (1995): Modern Electrochemistry
Type: book by Kluwer Academic / Plenum Publishers.

G. J. Bignold, A. D. Brewer, B. Hearn (1971): Specific conductivity and ionic product of water between 50 and 271 {[degree]C}
Type: article by Transactions of the Faraday Society.
link: http://dx.doi.org/10.1039/TF9716702419
Abstract:

The specific conductivity of high-purity water has been measured at temperatures between 51[degree] and {271[degree]C} along the saturated vapour pressure curve. Correction has been made for traces of contamination. The frequency dispersion of the impedance of the water-filled cell has been analyzed in terms of an equivalent electrical circuit. The data have been used to calculate the ionic product constant of water over this temperature range.

J. M. Berg, L. Stryer, J. L. Tymoczko (2007): Biochemie
Type: book by Spektrum Akademischer Verlag.

Kapitel 5

H. Beyer, W. Francke, W. Walter (2004): Lehrbuch der Organischen Chemie
Type: book by Hirzel, Stuttgart.

D. E. Metzler, C. M. Metzler (2000): Biochemistry Vol. 1. The Chemical Reactions of Living Cells
Type: book by Academic Press.

T. E. Creighton (1993): Proteins: Structures and Molecular Properties
Type: book by W. H. Freeman & Co Ltd.

P. Karlson, D. Doenecke, J. Koolman, G. Fuchs, W. Gerok (2005): Karlsons Biochemie und Pathobiochemie
Type: book by Thieme, Stuttgart.

P. McCaldon, P. Argos (1988): Oligopeptide biases in protein sequences and their use in predicting protein coding regions in nucleotide sequences
Type: article by Proteins.
doi: 10.1002/prot.340040204
link: http://www.ncbi.nlm.nih.gov/pubmed/3227018
Abstract:

We have examined oligopeptides with lengths ranging from 2 to 11 residues in protein sequences that show no obvious evolutionary relationship. All sequences in the Protein Identification Resource database were carefully classified by sensitive homology searches into superfamilies to obtain unbiased oligopeptide counts. The results, contrary to previous studies, show clear prejudices in protein sequences. The oligopeptide preferences were used to help decide the significance of sequence homologies and to improve the more general methods for detecting protein coding regions within nucleotide sequences.

J. M. Berg, L. Stryer, J. L. Tymoczko (2007): Biochemie
Type: book by Spektrum Akademischer Verlag.

Kapitel 6

K. E. van Holde, C. Johnson, P. S. Ho (2005): Principles of Physical Biochemistry
Type: book by {Prentice-Hall}.

B. Lee (1991): Solvent reorganization contribution to the transfer thermodynamics of small nonpolar molecules
Type: article by Biopolymers.
doi: 10.1002/bip.360310809
link: http://www.ncbi.nlm.nih.gov/pubmed/1782360
Abstract:

The experimental thermodynamic data for the dissolution of five simple hydrocarbon molecules in water were combined with the solute-solvent interaction energy from a computer simulation study to yield data on the enthalpy change of solvent reorganization. Similar data were generated for dissolving these same solute molecules in their respective neat solvents using the equilibrium vapor pressure and the heat of vaporization data for the pure liquid. The enthalpy and the free energy changes upon cavity formation were also estimated using the temperature dependence of the solute-solvent interaction energy. Both the enthalpy and T delta S for cavity formation rapidly increase with temperature in both solvent types, and the free energy of cavity formation can be reproduced accurately by the scaled particle theory over the entire temperature range in all cases. These results indicate that the characteristic structure formation around an inert solute molecule in water produces compensating changes in enthalpy and entropy, and that the hydrophobicity arises mainly from the difference in the excluded volume effect.

D. Hall, A. P. Minton (2003): Macromolecular crowding: qualitative and semiquantitative successes, quantitative challenges
Type: article by Biochimica Et Biophysica Acta.
link: http://www.ncbi.nlm.nih.gov/pubmed/12878031
Abstract:

The concept of excluded volume and the theory of effects of excluded volume on the equilibria and rates of macromolecular reactions in fluid media containing high total concentrations of macromolecules ('crowded' media) are summarized. Reports of experimental studies of crowding effects published during the last year are tabulated. Limitations of current excluded volume theory are discussed, and a determination is made of conditions under which this theory may and may not be validly applied. Recently suggested novel approaches to quantitative analysis of crowding phenomena, which may help to overcome some of the limitations of current theory, are summarized.

H. S. Ashbaugh, L. R. Pratt (2006): Colloquium: Scaled particle theory and the length scales of hydrophobicity
Type: article by Reviews of Modern Physics.
link: http://adsabs.harvard.edu/abs/2006RvMP...78..159A
Abstract:

Hydrophobic hydration plays a crucial role in self-assembly processes

over multiple length scales, from the microscopic origins of inert gas solubility in water, to the mesoscopic organization of proteins and surfactant structures, to macroscopic phase separation. Many theoretical studies focus on the molecularly detailed interactions between oil and water, but the extrapolation of molecular-scale models to larger-length-scale hydration phenomena is sometimes not warranted. Scaled particle theories are based upon an interpolative view of that microscopic{textless}--{textgreater}macroscopic issue. This Colloquium revisits the scaled particle theory proposed 30 years ago by Stillinger {[J.} Solution Chem. 2, 141 (1973)], adopts a practical generalization, and considers the implications for hydrophobic hydration in light of our current understanding. The generalization is based upon identifying a molecular length, implicit in previous applications of scaled particle models, which provides an effective radius for joining microscopic and macroscopic descriptions. It will be demonstrated that the generalized theory correctly reproduces many of the anomalous thermodynamic properties of hydrophobic hydration for molecularly sized solutes, including solubility minima and entropy convergence, successfully interpolates between the microscopic and macroscopic extremes, and provides new insights into the underlying molecular mechanisms. The model considered here serves as a reference for theories that bridge microscopic and macroscopic hydrophobic effects. The results are discussed in terms of length scales associated with component phenomena. In particular, first there is a discussion of the microscopic-macroscopic joining radius identified by the theory; then follows a discussion of the Tolman length that describes curvature corrections to a surface area model of hydrophobic hydration free energies and the length scales on which entropy convergence of hydration free energies are expected.

J. Cavanagh, W. J. Fairbrother, A. G. Palmer, N. J. Skelton, M. Rance (2006): Protein {NMR} Spectroscopy. Principles and Practice
Type: book by Academic Press.

P. C. Hiemenz, R. Rajagopalan (1997): Principles of Colloid and Surface Chemistry
Type: book by Marcel Dekker Inc.

D. T. Bowron (2004): Structure and interactions in simple solutions.
Type: article by Philosophical Transactions of the Royal Society B: Biological Sciences.
doi: 10.1098/rstb.2004.1496
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1693403&rendertype=abstract

H. Reiss, H. L. Frisch, J. L. Lebowitz (1959): Statistical Mechanics of Rigid Spheres
Type: article by The Journal of Chemical Physics.
doi: 10.1063/1.1730361
link: http://link.aip.org/link/?JCP/31/369/1

N. T. Southall, K. A. Dill, A. D. J. Haymet (2002): A View of the Hydrophobic Effect
Type: article by The Journal of Physical Chemistry B.
doi: 10.1021/jp020104r
link: http://dx.doi.org/10.1021/jp020104r

A. G. Ogston (1958): The spaces in a uniform random suspension of fibres
Type: article by Transactions of the Faraday Society.
link: http://dx.doi.org/10.1039/TF9585401754

J. L. Finney (2004): Water? What's so special about it?
Type: article by Philosophical Transactions of the Royal Society B: Biological Sciences.
doi: 10.1098/rstb.2004.1495
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1693413&rendertype=abstract

J. N. Israelachvili (1991): Intermolecular and Surface Forces: With Applications to Colloidal and Biological Systems
Type: book by Academic Pr Inc.

P. M. Chaikin, T. C. Lubensky (2000): Principles of Condensed Matter Physics
Type: book by Cambridge University Press.

T. E. Creighton (1993): Proteins: Structures and Molecular Properties
Type: book by W. H. Freeman & Co Ltd.

J. M. Ziman (1979): Models of Disorder: The Theoretical Physics of Homogeneously Disordered Systems
Type: book by Cambridge University Press.

S. Asakura, F. Oosawa (1954): On Interaction between Two Bodies Immersed in a Solution of Macromolecules
Type: article by Journal of Chemical Physics.
link: http://adsabs.harvard.edu/abs/1954JChPh..22.1255A
Abstract:

Not Available

T. C. Laurent, J. J. Killander (1964): A theory of gel filtration and its experimental verification
Type: article by Journal of Chromatography.
Abstract:

The separation of molecules according to size when chromatographed on granulated gels was explained in terms of sterical exclusion of the molecules from the gel grains.

The gel was assumed to be made up of a three-dimensional random network of fibers and the exclusion was calculated for spherical molecules of varying diameter. Theoretical values agreed with experimental data.

D. F. Evans, H. K. Wennerström (1999): The Colloidal Domain: Where Physics, Chemistry, Biology, and Technology Meet
Type: book by {Wiley-Vch}.

J. L. Lebowitz, E. Helfand, E. Praestgaard (1965): Scaled Particle Theory of Fluid Mixtures
Type: article by The Journal of Chemical Physics.
doi: 10.1063/1.1696842
link: http://link.aip.org/link/?JCP/43/774/1

V. A. Parsegian (2005): Van Der Waals Forces: A Handbook for Biologists, Chemists, Engineers, and Physicists
Type: book by Cambridge University Press.

C. Tanford (1980): The Hydrophobic Effect: Formation of Micelles and Biological Membranes
Type: book by John Wiley & Sons Inc.

S. Leikin, V. A. Parsegian, D. C. Rau, R. P. Rand (1993): Hydration Forces
Type: article by Annual Review of Physical Chemistry.
doi: 10.1146/annurev.pc.44.100193.002101
link: http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.pc.44.100193.002101

S. Marcelja, N. Radic (1976): Repulsion of interfaces due to boundary water
Type: article by Chemical Physics Letters.
link: http://adsabs.harvard.edu/abs/1976CPL....42..129M

R. S. Berry, S. A. Rice, J. Ross (2000): Physical Chemistry
Type: book by Oxford University Press.

Kapitel 7

J. SantaLucia, D. Hicks (2004): The thermodynamics of {DNA} structural motifs
Type: article by Annual Review of Biophysics and Biomolecular Structure.
doi: 10.1146/annurev.biophys.32.110601.141800
link: http://www.ncbi.nlm.nih.gov/pubmed/15139820
Abstract:

{DNA} secondary structure plays an important role in biology, genotyping diagnostics, a variety of molecular biology techniques, in vitro-selected {DNA} catalysts, nanotechnology, and {DNA-based} computing. Accurate prediction of {DNA} secondary structure and hybridization using dynamic programming algorithms requires a database of thermodynamic parameters for several motifs including {Watson-Crick} base pairs, internal mismatches, terminal mismatches, terminal dangling ends, hairpins, bulges, internal loops, and multibranched loops. To make the database useful for predictions under a variety of salt conditions, empirical equations for monovalent and magnesium dependence of thermodynamics have been developed. Bimolecular hybridization is often inhibited by competing unimolecular folding of a target or probe {DNA.} Powerful numerical methods have been developed to solve multistate-coupled equilibria in bimolecular and higher-order complexes. This review presents the current parameter set available for making accurate {DNA} structure predictions and also points to future directions for improvement.

P. Hänggi, P. Talkner, M. Borkovec (1990): Reaction-rate theory: fifty years after Kramers
Type: article by Reviews of Modern Physics.
link: http://adsabs.harvard.edu/abs/1990RvMP...62..251H
Abstract:

The calculation of rate coefficients is a discipline of nonlinear

science of importance to much of physics, chemistry, engineering, and biology. Fifty years after Kramers' seminal paper on thermally activated barrier crossing, the authors report, extend, and interpret much of our current understanding relating to theories of noise-activated escape, for which many of the notable contributions are originating from the communities both of physics and of physical chemistry. Theoretical as well as numerical approaches are discussed for single- and many-dimensional metastable systems (including fields) in gases and condensed phases. The role of many-dimensional transition-state theory is contrasted with Kramers' reaction-rate theory for moderate-to-strong friction; the authors emphasize the physical situation and the close connection between unimolecular rate theory and Kramers' work for weakly damped systems. The rate theory accounting for memory friction is presented, together with a unifying theoretical approach which covers the whole regime of weak-to-moderate-to-strong friction on the same basis (turnover theory). The peculiarities of noise-activated escape in a variety of physically different metastable potential configurations is elucidated in terms of the mean-first-passage-time technique. Moreover, the role and the complexity of escape in driven systems exhibiting possibly multiple, metastable stationary nonequilibrium states is identified. At lower temperatures, quantum tunneling effects start to dominate the rate mechanism. The early quantum approaches as well as the latest quantum versions of Kramers' theory are discussed, thereby providing a description of dissipative escape events at all temperatures. In addition, an attempt is made to discuss prominent experimental work as it relates to Kramers' reaction-rate theory and to indicate the most important areas for future research in theory and experiment.

C. L. Stevens, G. Felsenfeld (1964): The Conversion of {Two-Stranded} Poly {(A+U)} to {Three-Strand} Poly {(A+2U)} and Poly A by Heat
Type: article by Biopolymers 2.

K. E. van Holde, C. Johnson, P. S. Ho (2005): Principles of Physical Biochemistry
Type: book by {Prentice-Hall}.

H. Frauenfelder, F. Parak, R. D. Young (1988): Conformational substates in proteins
Type: article by Annual Review of Biophysics and Biophysical Chemistry.
doi: 10.1146/annurev.bb.17.060188.002315
link: http://www.ncbi.nlm.nih.gov/pubmed/3293595

J. I. Steinfeld, J. S. Francisco, W. L. Hase (1998): Chemical Kinetics and Dynamics
Type: book by Prentice Hall.

M. Karplus, J. A. McCammon (2002): Molecular dynamics simulations of biomolecules
Type: article by Nature Structural Biology.
doi: 10.1038/nsb0902-646
link: http://dx.doi.org/10.1038/nsb0902-646

P. W. Fenimore, H. Frauenfelder, B. H. McMahon, F. G. Parak (2002): Slaving: Solvent fluctuations dominate protein dynamics and functions
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
doi: 10.1073/pnas.212637899
link: http://www.pnas.org/content/99/25/16047.abstract
Abstract:

Protein motions are essential for function. Comparing protein processes with the dielectric fluctuations of the surrounding solvent shows that they fall into two classes: nonslaved and slaved. Nonslaved processes are independent of the solvent motions; their rates are determined by the protein conformation and vibrational dynamics. Slaved processes are tightly coupled to the solvent; their rates have approximately the same temperature dependence as the rate of the solvent fluctuations, but they are smaller. Because the temperature dependence is determined by the activation enthalpy, we propose that the solvent is responsible for the activation enthalpy, whereas the protein and the hydration shell control the activation entropy through the energy landscape. Bond formation is the prototype of nonslaved processes; opening and closing of channels are quintessential slaved motions. The prevalence of slaved motions highlights the importance of the environment in cells and membranes for the function of proteins.

R. Elber, M. Karplus (1990): Enhanced sampling in molecular dynamics: use of the time-dependent Hartree approximation for a simulation of carbon monoxide diffusion through myoglobin
Type: article by Journal of the American Chemical Society.
doi: 10.1021/ja00181a020
link: http://dx.doi.org/10.1021/ja00181a020

M. F. Perutz, A. J. Wilkinson, M. Paoli, G. G. Dodson (1998): {THE} {STEREOCHEMICAL} {MECHANISM} {OF} {THE} {COOPERATIVE} {EFFECTS} {IN} {HEMOGLOBIN} {REVISITED}
Type: article by Annual Review of Biophysics and Biomolecular Structure.
doi: 10.1146/annurev.biophys.27.1.1
link: http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biophys.27.1.1

R. H. Austin, K. W. Beeson, L. Eisenstein, H. Frauenfelder, I. C. Gunsalus (1975): Dynamics of ligand binding to myoglobin
Type: article by Biochemistry.
link: http://www.ncbi.nlm.nih.gov/pubmed/1191643
Abstract:

Myoglobin rebinding of carbon monoxide and dioxygen after photodissociation has been observed in the temperature range between 40 and 350 K. A system was constructed that records the change in optical absorption at 436 nm smoothly and without break between 2 musec and 1 ksec. Four different rebinding processes have been found. Between 40 and 160 K, a single process is observed. It is not exponential in time, but approximately given by N(t) = (1 + t/to)-n, where to and n are temperature-dependent, ligand-concentration independent, parameters. At about 170 K, a second and at 200 K, a third concentration-independent process emerge. At 210 K, a concentration-dependent process sets in. If myoglobin is embedded in a solid, only the first three can be seen, and they are all nonexponential. In a liquid glycerol-water solvent, rebinding is exponential. To interpret the data, a model is proposed in which the ligand molecule, on its way from the solvent to the binding site at the ferrous heme iron, encounters four barriers in succession. The barriers are tentatively identified with known features of myoglobin. By computer-solving the differential equation for the motion of a ligand molecule over four barriers, the rates for all important steps are obtained. The temperature dependences of the rates yield enthalpy, entropy, and free-energy changes at all barriers. The free-energy barriers at 310 K indicate how myoglobin achieves specificity and order. For carbon monoxide, the heights of these barriers increase toward the inside; carbon monoxide consequently is partially rejected at each of the four barriers. Dioxygen, in contrast, sees barriers of about equal height and moves smoothly toward the binding site. The entropy increases over the first two barriers, indicating a rupturing of bonds or displacement of residues, and then smoothly decreases, reaching a minimum at the binding site. The magnitude of the decrease over the innermost barrier implies participation of heme and/or protein. The nonexponential rebinding observed at low temperatures and in solid samples implies that the innermost barrier has a spectrum of activation energies. The shape of the spectrum has been determined; its existence can be explained by assuming the presence of many conformational states for myoglobin. In a liquid at temperatures above about 230 K, relaxation among conformational states occurs and rebinding becomes exponential.

J. Monod, J. Wyman, J. P. CHANGEUX (1965): {ON} {THE} {NATURE} {OF} {ALLOSTERIC} {TRANSITIONS:} A {PLAUSIBLE} {MODEL}
Type: article by Journal of Molecular Biology.
link: http://www.ncbi.nlm.nih.gov/pubmed/14343300

H. A. Kramers (1940): Brownian motion in a field of force and the diffusion model of chemical reactions
Type: article by Physica.
link: http://adsabs.harvard.edu/abs/1940Phy.....7..284K

T. E. Creighton (1993): Proteins: Structures and Molecular Properties
Type: book by W. H. Freeman & Co Ltd.

R. Hill (1936): Oxygen Dissociation Curves of Muscle Haemoglobin
Type: article by Royal Society of London Proceedings Series B.
link: http://adsabs.harvard.edu/abs/1936RSPSB.120..472H

B. H. Zimm, J. K. Bragg (1959): Theory of the Phase Transition between Helix and Random Coil in Polypeptide Chains
Type: article by The Journal of Chemical Physics.
doi: 10.1063/1.1730390
link: http://link.aip.org/link/?JCP/31/526/1

F. Colonna-Cesari, D. Perahia, M. Karplus, H. Eklund, C. I. Brädén, O. Tapia (1986): Interdomain motion in liver alcohol dehydrogenase. Structural and energetic analysis of the hinge bending mode
Type: article by The Journal of Biological Chemistry.
link: http://www.ncbi.nlm.nih.gov/pubmed/3771574
Abstract:

A study of the hinge bending mode in the enzyme liver alcohol dehydrogenase is made by use of empirical energy functions. The enzyme is a dimer, with each monomer composed of a coenzyme binding domain and a catalytic domain with a large cleft between the two. Superposition of the apoenzyme and holoenzyme crystal structures is used to determine a rigid rotation axis for closing of the cleft. It is shown that a rigid body transformation of the apoenzyme to the holoenzyme structure corresponds to a 10 degrees rotation of the catalytic domain about this axis. The rotation is not along the least-motion path for closing of the cleft but instead corresponds to the catalytic domain coming closer to the coenzyme binding domain by a sliding motion. Estimation of the energy associated with the interdomain motion of the apoenzyme over a range of 90 degrees (-40 to 50 degrees, where 0 degrees corresponds to the minimized crystal structure) demonstrates that local structural relaxation makes possible large-scale rotations with relatively small energy increments. A variety of structural rearrangements associated with the domain motion are characterized. They involve the hinge region residues that provide the covalent connections between the two domains and certain loop regions that are brought into contact by the rotation. Differences between the energy minimized and the holoenzyme structures point to the existence of alternative conformations for loops and to the importance of the ligands in the structural rearrangements.

J. Grotendorst, D. Marx, A. Muramatsu (2002): Quantum Simulations of Complex {Many-Body} Systems: From Theory to Algorithms {(G.} Sutmann {"Classical} Molecular Dynamics")
Type: book by Forschungszentrum Jülich.

P. Doty, J. T. Yang (1956): {POLYPEPTIDES.} {VII.} {POLY-γ-BENZYL-L-GLUTAMATE:} {THE} {HELIX-COIL} {TRANSITION} {IN} {SOLUTION1}
Type: article by Journal of the American Chemical Society.
doi: 10.1021/ja01583a070
link: http://dx.doi.org/10.1021/ja01583a070

H. J. Dyson, P. E. Wright (2005): Intrinsically unstructured proteins and their functions
Type: article by Nature Reviews. Molecular Cell Biology.
doi: 10.1038/nrm1589
link: http://www.ncbi.nlm.nih.gov/pubmed/15738986
Abstract:

Many gene sequences in eukaryotic genomes encode entire proteins or large segments of proteins that lack a well-structured three-dimensional fold. Disordered regions can be highly conserved between species in both composition and sequence and, contrary to the traditional view that protein function equates with a stable three-dimensional structure, disordered regions are often functional, in ways that we are only beginning to discover. Many disordered segments fold on binding to their biological targets (coupled folding and binding), whereas others constitute flexible linkers that have a role in the assembly of macromolecular arrays.

A. D. Jr. MacKerell, D. Bashford, M. Aepfelbacher, R. L. Jr. Dunbrack, J. D. Evanseck, M. J. Field, S. Fischer, J. Gao, H. Guo, S. Ha, D. Joseph-McCarthy, L. Kuchnir, K. Kuczera, F. T. K. Lau, C. Mattos, S. Michnick, T. Ngo, D. T. Nguyen, B. Prodhom, W. E. Reiher, B. Roux, M. Schlenkrich, J. C. Smith, R. Stote, J. Straub, M. Watanabe, J. Wiorkiewicz-Kuczera, D. Yin, M. Karplus (1998): {All-Atom} Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins
Type: article by The Journal of Physical Chemistry B.
doi: 10.1021/jp973084f
link: http://dx.doi.org/10.1021/jp973084f
Abstract:

New protein parameters are reported for the all-atom empirical energy function in the {CHARMM} program. The parameter evaluation was based on a self-consistent approach designed to achieve a balance between the internal (bonding) and interaction (nonbonding) terms of the force field and among the solventsolvent, solventsolute, and solutesolute interactions. Optimization of the internal parameters used experimental gas-phase geometries, vibrational spectra, and torsional energy surfaces supplemented with ab initio results. The peptide backbone bonding parameters were optimized with respect to data for N-methylacetamide and the alanine dipeptide. The interaction parameters, particularly the atomic charges, were determined by fitting ab initio interaction energies and geometries of complexes between water and model compounds that represented the backbone and the various side chains. In addition, dipole moments, experimental heats and free energies of vaporization, solvation and sublimation, molecular volumes, and crystal pressures and structures were used in the optimization. The resulting protein parameters were tested by applying them to noncyclic tripeptide crystals, cyclic peptide crystals, and the proteins crambin, bovine pancreatic trypsin inhibitor, and carbonmonoxy myoglobin in vacuo and in crystals. A detailed analysis of the relationship between the alanine dipeptide potential energy surface and calculated protein phi, chi angles was made and used in optimizing the peptide group torsional parameters. The results demonstrate that use of ab initio structural and energetic data by themselves are not sufficient to obtain an adequate backbone representation for peptides and proteins in solution and in crystals. Extensive comparisons between molecular dynamics simulations and experimental data for polypeptides and proteins were performed for both structural and dynamic properties. Energy minimization and dynamics simulations for crystals demonstrate that the latter are needed to obtain meaningful comparisons with experimental crystal structures. The presented parameters, in combination with the previously published {CHARMM} all-atom parameters for nucleic acids and lipids, provide a consistent set for condensed-phase simulations of a wide variety of molecules of biological interest.

J. Marmur, P. Doty (1959): Heterogeneity in Deoxyribonucleic Acids: I. Dependence on Composition of the Configurational Stability of Deoxyribonucleic Acids
Type: article by Nature.
doi: 10.1038/1831427a0
link: http://dx.doi.org/10.1038/1831427a0

M. F. Perutz (1970): Stereochemistry of Cooperative Effects in Haemoglobin: {Haem-Haem} Interaction and the Problem of Allostery
Type: article by Nature.
doi: 10.1038/228726a0
link: http://dx.doi.org/10.1038/228726a0

K. A. Dill (1999): Polymer principles and protein folding.
Type: article by Protein Science : A Publication of the Protein Society.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2144345&rendertype=abstract

J. A. Subirana, P. Doty (1966): Kinetics of renaturation of denatured {DNA.} I. Spectrophotometric results
Type: article by Biopolymers.
doi: 10.1002/bip.1966.360040204
link: http://dx.doi.org/10.1002/bip.1966.360040204
Abstract:

The kinetics of renaturation of heat- or formamide-denatured {DNA} have been studied by following the change of optical density at a constant temperature. Solvents of different ionic strength and various {DNA} samples have been used. At the lower ionic strengths studied, the reaction follows second-order kinetics, substantiating the hypothesis that strands of native {DNA} separate upon denaturation and recombine during renaturation. As the ionic strength is increased at a constant temperature, the reaction deviates from simple second-order behavior. This appears to be the result of the inhibition to rewinding caused by short helical segments in the denatured {DNA} which are more stable at the higher ionic strenth.

D. E. Anderson, R. J. Peters, B. Wilk, D. A. Agard (1999): Alpha-lytic protease precursor: characterization of a structured folding intermediate
Type: article by Biochemistry.
doi: 10.1021/bi982165e
link: http://www.ncbi.nlm.nih.gov/pubmed/10200160
Abstract:

The bacterial alpha-lytic protease {(alphaLP)} is synthesized as a precursor containing a large N-terminal pro region {(Pro)} transiently required for correct folding of the protease {[Silen,} J. L., and Agard, D. A. (1989) Nature 341, 462-464]. Upon folding, the precursor is autocatalyticly cleaved to yield a tight-binding inhibitory complex of the pro region and the fully folded protease {(Pro/alphaLP).} An in vitro purification and refolding protocol has been developed for production of the disulfide-bonded precursor. A combination of spectroscopic approaches have been used to compare the structure and stability of the precursor with either the {Pro/alphaLP} complex or isolated Pro. The precursor and complex have significant similarities in secondary structure but some differences in tertiary structure, as well as a dramatic difference in stability. Correlations with isolated Pro suggest that the pro region part of the precursor is fully folded and acts to stabilize and structure the {alphaLP} region. Precursor folding is shown to be biphasic with the fast phase matching the rate of pro region folding. Further, the rate-limiting step in oxidative folding is formation of the disulfide bonds and autocatalytic processing occurs rapidly thereafter. These studies suggests a model in which the pro region folds first and catalyzes folding of the protease domain, forming the active site and finally causing autocatalytic cleavage of the bond separating pro region and protease. This last processing step is critical as it allows the protease N-terminus to rearrange, providing the majority of net stabilization of the product {Pro/alphaLP} complex.

C. J. Tsai, S. Kumar, B. Ma, R. Nussinov (1999): Folding funnels, binding funnels, and protein function
Type: article by Protein Science: A Publication of the Protein Society.
doi: 10.1110/ps.8.6.1181
link: http://www.ncbi.nlm.nih.gov/pubmed/10386868
Abstract:

Folding funnels have been the focus of considerable attention during the last few years. These have mostly been discussed in the general context of the theory of protein folding. Here we extend the utility of the concept of folding funnels, relating them to biological mechanisms and function. In particular, here we describe the shape of the funnels in light of protein synthesis and folding; flexibility, conformational diversity, and binding mechanisms; and the associated binding funnels, illustrating the multiple routes and the range of complexed conformers. Specifically, the walls of the folding funnels, their crevices, and bumps are related to the complexity of protein folding, and hence to sequential vs. nonsequential folding. Whereas the former is more frequently observed in eukaryotic proteins, where the rate of protein synthesis is slower, the latter is more frequent in prokaryotes, with faster translation rates. The bottoms of the funnels reflect the extent of the flexibility of the proteins. Rugged floors imply a range of conformational isomers, which may be close on the energy landscape. Rather than undergoing an induced fit binding mechanism, the conformational ensembles around the rugged bottoms argue that the conformers, which are most complementary to the ligand, will bind to it with the equilibrium shifting in their favor. Furthermore, depending on the extent of the ruggedness, or of the smoothness with only a few minima, we may infer nonspecific, broad range vs. specific binding. In particular, folding and binding are similar processes, with similar underlying principles. Hence, the shape of the folding funnel of the monomer enables making reasonable guesses regarding the shape of the corresponding binding funnel. Proteins having a broad range of binding, such as proteolytic enzymes or relatively nonspecific endonucleases, may be expected to have not only rugged floors in their folding funnels, but their binding funnels will also behave similarly, with a range of complexed conformations. Hence, knowledge of the shape of the folding funnels is biologically very useful. The converse also holds: If kinetic and thermodynamic data are available, hints regarding the role of the protein and its binding selectivity may be obtained. Thus, the utility of the concept of the funnel carries over to the origin of the protein and to its function.

D. Thorn Leeson, D. A. Wiersma, K. Fritsch, J. Friedrich (1997): The Energy Landscape of Myoglobin: An Optical Study
Type: article by The Journal of Physical Chemistry B.
doi: 10.1021/jp970908k
link: http://dx.doi.org/10.1021/jp970908k
Abstract:

In this paper we demonstrate how the potential energy surface of a protein, which determines its conformational degrees of freedom, can be constructed from a series of advanced nonlinear optical experiments. The energy landscape of myoglobin was probed by studying its low-temperature structural dynamics, using several spectral hole burning and photon echo techniques. The spectral diffusion of the heme group of the protein was studied on a time scale ranging from nanoseconds to several days while covering a temperature range from 100 {mK} to 23 K. The spectral line broadening, as measured in three-pulse stimulated photon echo experiments, occurs in a stepwise fashion, while the exact time dependence of the line width is critically dependent on temperature. From these results we obtained the energy barriers between the conformational states of the protein. Aging time dependent hole-burning experiments show that, at 100 {mK,} it takes several days for the protein to reach thermal equilibrium. When, after this period a spectral hole is burned, the line broadening induced by well-defined temperature cycles is partly reversed over a period of several hours. From this we conclude that a rough structure is superimposed on the overall shape of the potential energy surface of the protein. By combining the hole burning and photon echo results, we construct a detailed image of this energy landscape, supporting the general concept of a structural hierarchy. More specifically, we show that the number of conformational substates in the lower hierarchical tiers is much lower than was previously anticipated and, in fact, is comparable to the number of taxonomic substates.

Y. S. Lazurkin, M. D. Frank-Kamenetskii, E. N. Trifonov (1970): Melting of {DNA:} its study and application as a research method
Type: article by Biopolymers.
doi: 10.1002/bip.1970.360091102
link: http://www.ncbi.nlm.nih.gov/pubmed/4922326

H. Risken, T. Frank (1996): The {Fokker-Planck} Equation: Methods of Solutions and Applications
Type: book by Springer, Berlin.

J. Applequist (1963): On the {Helix-Coil} Equilibrium in Polypeptides
Type: article by The Journal of Chemical Physics.
doi: 10.1063/1.1733787
link: http://link.aip.org/link/?JCP/38/934/1

F. Schwabl (2006): Statistische Mechanik: Mit 186 Aufgaben
Type: book by Springer, Berlin.

C. R. Cantor, P. R. Schimmel (1980): Biophysical Chemistry: Part {III:} The Behavior of Biological Macromolecules: Pt.3
Type: book by W. H. Freeman & Co Ltd.

D. Hamada, S. Segawa, Y. Goto (1996): Non-native [alpha]-helical intermediate in the refolding of [beta]-lactoglobulin, a predominantly [beta]-sheet protein
Type: article by Nature Structural Biology.
doi: 10.1038/nsb1096-868
link: http://dx.doi.org/10.1038/nsb1096-868

F. Chiti, C. M. Dobson (2006): Protein misfolding, functional amyloid, and human disease
Type: article by Annual Review of Biochemistry.
doi: 10.1146/annurev.biochem.75.101304.123901
link: http://www.ncbi.nlm.nih.gov/pubmed/16756495
Abstract:

Peptides or proteins convert under some conditions from their soluble forms into highly ordered fibrillar aggregates. Such transitions can give rise to pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. In this review, we identify the diseases known to be associated with formation of fibrillar aggregates and the specific peptides and proteins involved in each case. We describe, in addition, that living organisms can take advantage of the inherent ability of proteins to form such structures to generate novel and diverse biological functions. We review recent advances toward the elucidation of the structures of amyloid fibrils and the mechanisms of their formation at a molecular level. Finally, we discuss the relative importance of the common main-chain and side-chain interactions in determining the propensities of proteins to aggregate and describe some of the evidence that the oligomeric fibril precursors are the primary origins of pathological behavior.

J. D. Bryngelson, J. N. Onuchic, N. D. Socci, P. G. Wolynes (1995): Funnels, pathways, and the energy landscape of protein folding: a synthesis
Type: article by Proteins: Structure, Function and Genetics.
doi: 10.1002/prot.340210302
link: http://www.ncbi.nlm.nih.gov/pubmed/7784423
Abstract:

The understanding, and even the description of protein folding is impeded by the complexity of the process. Much of this complexity can be described and understood by taking a statistical approach to the energetics of protein conformation, that is, to the energy landscape. The statistical energy landscape approach explains when and why unique behaviors, such as specific folding pathways, occur in some proteins and more generally explains the distinction between folding processes common to all sequences and those peculiar to individual sequences. This approach also gives new, quantitative insights into the interpretation of experiments and simulations of protein folding thermodynamics and kinetics. Specifically, the picture provides simple explanations for folding as a two-state first-order phase transition, for the origin of metastable collapsed unfolded states and for the curved Arrhenius plots observed in both laboratory experiments and discrete lattice simulations. The relation of these quantitative ideas to folding pathways, to uniexponential vs. multiexponential behavior in protein folding experiments and to the effect of mutations on folding is also discussed. The success of energy landscape ideas in protein structure prediction is also described. The use of the energy landscape approach for analyzing data is illustrated with a quantitative analysis of some recent simulations, and a qualitative analysis of experiments on the folding of three proteins. The work unifies several previously proposed ideas concerning the mechanism protein folding and delimits the regions of validity of these ideas under different thermodynamic conditions.

F. Parak, E. W. Knapp, D. Kucheida (1982): Protein dynamics: Mössbauer spectroscopy on deoxymyoglobin crystals
Type: article by Journal of Molecular Biology.
doi: 10.1016/0022-2836(82)90285-6
link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WK7-4DM18DV-8T&_user=10&_coverDate=10%2F15%2F1982&_alid=932008354&_rdoc=1&_fmt=high&_orig=search&_cdi=6899&_docanchor=&view=c&_ct=1&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=e7cc47bc6ca6e3a5b22457a99bd6b203
Abstract:

Mössbauer absorption experiments on {57Fe} of deoxygenated myoglobin crystals and on K4 {57Fe(CN)6} dissolved in the water of metmyoglobin crystals were performed over a large temperature range. At low temperatures the mean square displacements, x2, of the iron indicate solid-like behaviour of the whole system, whereas at higher temperatures protein-specific modes of motion contribute to x2{textgreater}. The protein dynamics are correlated with the mobility of the water within the protein crystals. A Brownian oscillator is used to model the protein-specific modes of motion measured at the {57Fe} nucleus. Three modes are necessary for understanding the Mössbauer spectrum. Two of them correspond to an extremely overdamped Brownian oscillator. The third mode can be understood as quasi-free diffusion. Whereas the protein molecule is frozen in conformational substates in the low temperature regime, it reaches transition states with a finite probability in the high temperature regime. The surface water mediates a possible trigger mechanism that switches on protein dynamics within a narrow temperature interval. Results from Mössbauer spectroscopy and from X-ray structure analysis are compared. *1 This work was supported by the Deutsche Forschungs Gemeinschaft {(Pa} 178/8 and {SFB} 143 C2).

C. Bossa, M. Anselmi, D. Roccatano, A. Amadei, B. Vallone, M. Brunori, A. Di Nola (2004): Extended molecular dynamics simulation of the carbon monoxide migration in sperm whale myoglobin
Type: article by Biophysical Journal.
doi: 10.1529/biophysj.103.037432
link: http://www.ncbi.nlm.nih.gov/pubmed/15189882
Abstract:

We report the results of an extended molecular dynamics simulation on the migration of photodissociated carbon monoxide in wild-type sperm whale myoglobin. Our results allow following one possible ligand migration dynamics from the distal pocket to the Xe1 cavity via a path involving the other xenon binding cavities and momentarily two additional packing defects along the pathway. Comparison with recent time resolved structural data obtained by Laue crystallography with subnanosecond to millisecond resolution shows a more than satisfactory agreement. In fact, according to time resolved crystallography, {CO,} after photolysis, can occupy the Xe1 and Xe4 cavities. However, no information on the trajectory of the ligand from the distal pocket to the Xe1 is available. Our results clearly show one possible path within the protein. In addition, although our data refer to a single trajectory, the local dynamics of the ligand in each cavity is sufficiently equilibrated to obtain local structural and thermodynamic information not accessible to crystallography. In particular, we show that the {CO} motion and the protein fluctuations are strictly correlated: free energy calculations of the migration between adjacent cavities show that the migration is not a simple diffusion but is kinetically or thermodynamically driven by the collective motions of the protein; conversely, the protein fluctuations are influenced by the ligand in such a way that the opening/closure of the passage between adjacent cavities is strictly correlated to the presence of {CO} in its proximity. The compatibility between time resolved crystallographic experiments and molecular dynamics simulations paves the way to a deeper understanding of the role of internal dynamics and packing defects in the control of ligand binding in heme proteins.

Kapitel 8

B. Alberts, A. Johnson, P. Walter, J. Lewis, M. Raff, K. Roberts (2008): Molecular Biology of the Cell
Type: book by Taylor & Francis.

R. Cahn, W. Ludwig (1985): Theorie der Wärme.
Type: book by Springer, Berlin.

H. G. Hansma, J. H. Hoh (1994): Biomolecular Imaging with the Atomic Force Microscope
Type: article by Annual Review of Biophysics and Biomolecular Structure.
doi: 10.1146/annurev.bb.23.060194.000555
link: http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.bb.23.060194.000555

D. T. Gillespie (1996): The mathematics of Brownian motion and Johnson noise
Type: article by American Journal of Physics.
doi: 10.1119/1.18210
link: http://link.aip.org/link/?AJP/64/225/1

N. Voiculetz, I. Motoc (1993): Specific Interactions and Biological Recognition Processes
Type: book by {CRC} Press Inc.

M. Radermacher Single molecules feel the force
Type: misc
link: http://physicsworld.com/cws/article/print/955
It was published through http://physicsworld.com/cws/article/print/955
Abstract:

Biophysicists are now able to study a whole host of living processes with unprecedented accuracy thanks to a microscope normally associated with surface science.

O. Livnah, E. A. Bayer, M. Wilchek, J. L. Sussman (1993): Three-dimensional structures of avidin and the avidin-biotin complex
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
doi: VL - 90
link: http://www.pnas.org/content/90/11/5076.abstract
Abstract:

The crystal structures of a deglycosylated form of the egg-white glycoprotein avidin and of its complex with biotin have been determined to 2.6 and 3.0 A, respectively. The structures reveal the amino acid residues critical for stabilization of the tetrameric assembly and for the exceptionally tight binding of biotin. Each monomer is an eight-stranded antiparallel beta-barrel, remarkably similar to that of the genetically distinct bacterial analog streptavidin. As in streptavidin, binding of biotin involves a highly stabilized network of polar and hydrophobic interactions. There are, however, some differences. The presence of additional hydrophobic and hydrophilic groups in the binding site of avidin (which are missing in streptavidin) may account for its higher affinity constant. Two amino acid substitutions are proposed to be responsible for its susceptibility to denaturation relative to streptavidin. Unexpectedly, a residual N-acetylglucosamine moiety was detected in the deglycosylated avidin monomer by difference Fourier synthesis.

R. Merkel, P. Nassoy, A. Leung, K. Ritchie, E. Evans (1999): Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy
Type: article by Nature.
doi: 10.1038/16219
link: http://dx.doi.org/10.1038/16219

B. Essevaz-Roulet, U. Bockelmann, F. Heslot (1997): Mechanical separation of the complementary strands of {DNA}
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
link: http://www.ncbi.nlm.nih.gov/pubmed/9342340
Abstract:

We describe the mechanical separation of the two complementary strands of a single molecule of bacteriophage lambda {DNA.} The 3' and 5' extremities on one end of the molecule are pulled progressively apart, and this leads to the opening of the double helix. The typical forces along the opening are in the range of 10-15 {pN.} The separation force signal is shown to be related to the local {GC} vs. {AT} content along the molecule. Variations of this content on a typical scale of 100-500 bases are presently detected.

L. Bergmann, C. Schaefer (2008): Lehrbuch der Experimentalphysik: Lehrbuch der Experimentalphysik 1. Mechanik - Akkustik - Wärme: Bd 1: Band 1
Type: book by Gruyter.

M. P. Sheetz (1998): Laser Tweezers in Cell Biology
Type: book by Academic Press.

F. Colonna-Cesari, D. Perahia, M. Karplus, H. Eklund, C. I. Brädén, O. Tapia (1986): Interdomain motion in liver alcohol dehydrogenase. Structural and energetic analysis of the hinge bending mode
Type: article by The Journal of Biological Chemistry.
link: http://www.ncbi.nlm.nih.gov/pubmed/3771574
Abstract:

A study of the hinge bending mode in the enzyme liver alcohol dehydrogenase is made by use of empirical energy functions. The enzyme is a dimer, with each monomer composed of a coenzyme binding domain and a catalytic domain with a large cleft between the two. Superposition of the apoenzyme and holoenzyme crystal structures is used to determine a rigid rotation axis for closing of the cleft. It is shown that a rigid body transformation of the apoenzyme to the holoenzyme structure corresponds to a 10 degrees rotation of the catalytic domain about this axis. The rotation is not along the least-motion path for closing of the cleft but instead corresponds to the catalytic domain coming closer to the coenzyme binding domain by a sliding motion. Estimation of the energy associated with the interdomain motion of the apoenzyme over a range of 90 degrees (-40 to 50 degrees, where 0 degrees corresponds to the minimized crystal structure) demonstrates that local structural relaxation makes possible large-scale rotations with relatively small energy increments. A variety of structural rearrangements associated with the domain motion are characterized. They involve the hinge region residues that provide the covalent connections between the two domains and certain loop regions that are brought into contact by the rotation. Differences between the energy minimized and the holoenzyme structures point to the existence of alternative conformations for loops and to the importance of the ligands in the structural rearrangements.

M. Rief, J. M. Fernandez, H. E. Gaub (1998): Elastically Coupled {Two-Level} Systems as a Model for Biopolymer Extensibility
Type: article by Physical Review Letters.
link: http://adsabs.harvard.edu/abs/1998PhRvL..81.4764R
Abstract:

We present Monte Carlo simulations for the elasticity of biopolymers

consisting of segments that can undergo conformational transitions. Based on the thermodynamics of an elastically coupled two-level system, the probability for a transition and a related change in length of each segment was calculated. Good agreement between this model description and measured data was found for both the polysaccharide dextran where the conformational changes are fast and the muscle protein titin where the marked rate dependence of the transition forces could be explained by nonequilibrium processes.

M. Rief, M. Gautel, F. Oesterhelt, J. M. Fernandez, H. E. Gaub (1997): Reversible Unfolding of Individual Titin Immunoglobulin Domains by {AFM}
Type: article by Science.
doi: 10.1126/science.276.5315.1109
link: http://www.sciencemag.org/cgi/content/abstract/276/5315/1109

R. Alon, D. A. Hammer, T. A. Springer (1995): Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow
Type: article by Nature.
doi: 10.1038/374539a0
link: http://dx.doi.org/10.1038/374539a0

L. Tskhovrebova, J. Trinick, J. A. Sleep, R. M. Simmons (1997): Elasticity and unfolding of single molecules of the giant muscle protein titin
Type: article by Nature.
doi: 10.1038/387308a0
link: http://dx.doi.org/10.1038/387308a0

D. E. Koshland (1958): Application of a Theory of Enzyme Specificity to Protein Synthesis
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
doi: VL - 44
link: http://www.pnas.org/content/44/2/98.short

D. A. Simson, M. Strigl, M. Hohenadl, R. Merkel (1999): Statistical Breakage of Single Protein {A-IgG} Bonds Reveals Crossover from Spontaneous to {Force-Induced} Bond Dissociation
Type: article by Physical Review Letters.
link: http://adsabs.harvard.edu/abs/1999PhRvL..83..652S
Abstract:

Dynamic force spectroscopy was applied to single specific bonds between

immunoglobulins of type G and protein A, a staphylococcal receptor for {IgG.} The resulting spectra of yield forces indicated the crossover from force induced to spontaneous bond dissociation. Moreover, failure of unloaded bonds was observed directly. Extrapolation to vanishing loading rate and direct observation yielded coinciding results.

G. I. Bell (1978): Models for the specific adhesion of cells to cells
Type: article by Science.
doi: 10.1126/science.347575
link: http://www.sciencemag.org/cgi/content/abstract/200/4342/618
Abstract:

A theoretical framework is proposed for the analysis of adhesion between cells or of cells to surfaces when the adhesion is mediated by reversible bonds between specific molecules such as antigen and antibody, lectin and carbohydrate, or enzyme and substrate. From a knowledge of the reaction rates for reactants in solution and of their diffusion constants both in solution and on membranes, it is possible to estimate reaction rates for membrane-bound reactants. Two models are developed for predicting the rate of bond formation between cells and are compared with experiments. The force required to separate two cells is shown to be greater than the expected electrical forces between cells, and of the same order of magnitude as the forces required to pull gangliosides and perhaps some integral membrane proteins out of the cell membrane.

E. Evans, K. Ritchie (1997): Dynamic strength of molecular adhesion bonds.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1184350&rendertype=abstract

T. A. Steitz, M. Shoham, W. S. Bennett (1981): Structural Dynamics of Yeast Hexokinase During Catalysis
Type: article by Royal Society of London Philosophical Transactions Series B.
link: http://adsabs.harvard.edu/abs/1981RSPTB.293...43S
Abstract:

The binding of the substrate glucose to yeast hexokinase results in a

substantial enzyme conformational change that is essential for catalysis and may be important for the enzyme's specificity, as well as the control of its activity. From high-resolution crystal structures of the monomeric enzyme crystallized both in the presence and in the absence of glucose, we find that glucose binds into the deep cleft that separates the molecule into two lobes and causes these two lobes to move together and close off the cleft. The structure of the hexokinase crystallized in the presence of xylose and {ADP} is being determined at low resolution. In this crystal form, the enzyme was thought to be in the conformation of the ternary complex. However, a low-resolution structure of this crystal form shows clearly that the enzyme is in the `open' form and is not a ternary complex. Crystals of the A isozyme with glucose and {ADP} may be. Further, chemically sequenced tryptic peptides are being incorporated into the model obtained by crystallographic refinement at 2.1 A resolution. Completion of the sequence and the structure of the ternary complex should allow a detailed description of the enzymatic mechanism of this kinase and the role of substrate-induced conformational changes in catalysis and control.

M. Carrion-Vazquez, A. F. Oberhauser, S. B. Fowler, P. E. Marszalek, S. E. Broedel, J. Clarke, J. M. Fernandez (1999): Mechanical and chemical unfolding of a single protein: A comparison
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
doi: VL - 96
link: http://www.pnas.org/content/96/7/3694.abstract
Abstract:

Is the mechanical unraveling of protein domains by atomic force microscopy {(AFM)} just a technological feat or a true measurement of their unfolding? By engineering a protein made of tandem repeats of identical Ig modules, we were able to get explicit {AFM} data on the unfolding rate of a single protein domain that can be accurately extrapolated to zero force. We compare this with chemical unfolding rates for untethered modules extrapolated to 0 M denaturant. The unfolding rates obtained by the two methods are the same. Furthermore, the transition state for unfolding appears at the same position on the folding pathway when assessed by either method. These results indicate that mechanical unfolding of a single protein by {AFM} does indeed reflect the same event that is observed in traditional unfolding experiments. The way is now open for the extensive use of {AFM} to measure folding reactions at the single-molecule level. Single-molecule {AFM} recordings have the added advantage that they define the reaction coordinate and expose rare unfolding events that cannot be observed in the absence of chemical denaturants.

P. R. Kuser, S. Krauchenco, O. A. C. Antunes, I. Polikarpov (2000): The High Resolution Crystal Structure of Yeast Hexokinase {PII} with the Correct Primary Sequence Provides New Insights into Its Mechanism of Action
Type: article by Journal of Biological Chemistry.
doi: 10.1074/jbc.M910412199
link: http://www.jbc.org/cgi/content/abstract/275/27/20814
Abstract:

Hexokinase is the first enzyme in the glycolytic pathway, catalyzing the transfer of a phosphoryl group from {ATP} to glucose to form glucose 6-phosphate and {ADP.} Two yeast hexokinase isozymes are known, namely {PI} and {PII.} The crystal structure of yeast hexokinase {PII} from Saccharomyces cerevisiae without substrate or competitive inhibitor is determined and refined in a tetragonal crystal form at {2.2-A} resolution. The folding of the peptide chain is very similar to that of Schistosoma mansoni and previous yeast hexokinase models despite only 30% sequence identity between them. Distinct differences in conformation are found that account for the absence of glucose in the binding site. Comparison of the current model with S. mansoni and yeast hexokinase {PI} structures both complexed with glucose shows in atomic detail the rigid body domain closure and specific loop movements as glucose binds. A hydrophobic channel formed by strictly conserved hydrophobic residues in the small domain of the hexokinase is identified. The channel's mouth is close to the active site and passes through the small domain to its surface. The possible role of the observed channel in proton transfer is discussed.

J. DeChancie, K. N. Houk (2007): The Origins of Femtomolar {Protein–Ligand} Binding: Hydrogen Bond Cooperativity and Desolvation Energetics in the {Biotin–(Strept)Avidin} Binding Site
Type: article by Journal of the American Chemical Society.
doi: 10.1021/ja066950n
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2527462

U. Bockelmann, B. Essevaz-Roulet, F. Heslot (1997): Molecular {Stick-Slip} Motion Revealed by Opening {DNA} with Piconewton Forces
Type: article by Physical Review Letters.
doi: 10.1103/PhysRevLett.79.4489
link: http://link.aps.org/abstract/PRL/v79/p4489
Abstract:

We have pulled apart the two strands of a {DNA} double helix. The forces measured during this process show a sequence specific variation on the piconewton scale. Opening two helical molecules with the same sequence from opposite sides gives two signatures which are not simply related by symmetry. In a theoretical model, this is explained as a molecular stick-slip motion which does not involve instabilities and is determined by the sequence.

S. Chu (1992): Laser Trapping of neutral Particles
Type: article by Scientific American.
Abstract:

Lasers can be used to trap and manipulate electrically neutral particles. These techniques have allowed scientists to cool vapors to near absolute zero, develop new atomic clocks, and stretch single molecules of {DNA}

M. S. Z. Kellermayer, S. B. Smith, H. L. Granzier, C. Bustamante (1997): {Folding-Unfolding} Transitions in Single Titin Molecules Characterized with Laser Tweezers
Type: article by Science.
doi: 10.1126/science.276.5315.1112
link: http://www.sciencemag.org/cgi/content/abstract/276/5315/1112

J. M. Berg, L. Stryer, J. L. Tymoczko (2007): Biochemie
Type: book by Spektrum Akademischer Verlag.

E. Fischer (1894): Einfluss der Configuration auf die Wirkung der Enzyme
Type: article by Berichte der deutschen chemischen Gesellschaft.
link: http://dx.doi.org/10.1002/cber.18940270364
Abstract:

No Abstract.

M. Radmacher (1999): Single molecules feel the force
Type: article by Physics World.

K. Berg-Sørensen, H. Flyvbjerg (2004): Power spectrum analysis for optical tweezers
Type: article by Review of Scientific Instruments.
link: http://adsabs.harvard.edu/abs/2004RScI...75..594B
Abstract:

The force exerted by an optical trap on a dielectric bead in a fluid is

often found by fitting a Lorentzian to the power spectrum of Brownian motion of the bead in the trap. We present explicit functions of the experimental power spectrum that give the values of the parameters fitted, including error bars and correlations, for the best such χ2 fit in a given frequency range. We use these functions to determine the information content of various parts of the power spectrum, and find, at odds with lore, much information at relatively high frequencies. Applying the method to real data, we obtain perfect fits and calibrate tweezers with less than 1% error when the trapping force is not too strong. Relatively strong traps have power spectra that cannot be fitted properly with any Lorentzian, we find. This underscores the need for better understanding of the power spectrum than the Lorentzian provides. This is achieved using old and new theory for Brownian motion in an incompressible fluid, and new results for a popular photodetection system. The trap and photodetection system are then calibrated simultaneously in a manner that makes optical tweezers a tool of precision for force spectroscopy, local viscometry, and probably other applications.

Kapitel 9

T. M. Allen, P. R. Cullis (2004): Drug Delivery Systems: Entering the Mainstream
Type: article by Science.
doi: 10.1126/science.1095833
link: http://www.sciencemag.org/cgi/content/abstract/303/5665/1818
Abstract:

Drug delivery systems {(DDS)} such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate {DDS} have been overcome, with several {DDS} formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of {DDS} for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.

G. Blobel (1980): Intracellular protein topogenesis
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=348522&rendertype=abstract

M. Tanaka, E. Sackmann (2005): Polymer-supported membranes as models of the cell surface
Type: article by Nature.
doi: 10.1038/nature04164
link: http://dx.doi.org/10.1038/nature04164

S. L. Hardt (1979): Rates of diffusion controlled reactions in one, two and three dimensions
Type: article by Biophysical Chemistry.
link: http://www.ncbi.nlm.nih.gov/pubmed/16997220
Abstract:

The dimensionality of diffusion may markedly affect the rate and economy of diffusion controlled reactions. Moreover, the degree of dependence of the steady state rate of these reactions on the concentration of each of the two reacting species is also dictated by the dimensionality and it ranges from linear dependence in the three dimensional case to a nearly square dependence in the one dimensional case. These theoretical observations emerge from a direct analysis of the steady state diffusion controlled rates which are derived here using a simple straightforward approach. This approach is based on the conjecture that in the steady state the rate of diffusional encounters between the two reaction partners equals to the sum of the encounter rates of two independent processes which are obtained by alternately immobilizing one of the reaction partners while the other partner diffuses freely. Unlike Smoluchowski's classical approach, the presented point of view permits to obtain in a unified fashion reaction rates for all dimensionalities.

E. Sackmann, E. Bausch, L. Vonna (2002): Physics of Composite Cell Membrane and Actin Based Cytoskeleton
Type: incollection
link: http://dx.doi.org/10.1007/3-540-45701-1_7
Abstract:

The composite cell envelope is an impressive example of nature’s strategy to design complex materials and machineries with

unique and stunning physical properties by self-assembly of hierarchical structures. The most simple prototype of a composite cell membrane is the envelope (often called plasma membrane) of red blood cells.

E. Townes-Anderson, R. F. Dacheux, E. Raviola (1988): Rod photoreceptors dissociated from the adult rabbit retina
Type: article by Journal of Neuroscience.
link: http://www.jneurosci.org/cgi/content/abstract/8/1/320

J. A. F. Op den Kamp (1979): Lipid Asymmetry in Membranes
Type: article by Annual Review of Biochemistry.
doi: 10.1146/annurev.bi.48.070179.000403
link: http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.bi.48.070179.000403

R. Lipowsky, E. Sackmann (1996): Architecture and Function. Handbook of Biological Physics Vol I
Type: book by Elsevier.
Abstract:

The first volume of the Handbook deals with the amazing world of biomembranes and lipid bilayers. Part A describes all aspects related to the morphology of these membranes, beginning with the complex architecture of biomembranes, continues with a description of the bizarre morphology of lipid bilayers and concludes with technological applications of these membranes. The first two chapters deal with biomembranes, providing an introduction to the membranes of eucaryotes and a description of the evolution of membranes. The following chapters are concerned with different aspects of lipids including the physical properties of model membranes composed of lipid-protein mixtures, lateral phase separation of lipids and proteins and measurement of lipid-protein bilayer diffusion. Other chapters deal with the flexibility of fluid bilayers, the closure of bilayers into vesicles which attain a large variety of different shapes, and applications of lipid vesicles and liposomes.

Part B covers membrane adhesion, membrane fusion and the interaction of biomembranes with polymer networks such as the cytoskeleton. The first two chapters of this part discuss the generic interactions of membranes from the conceptual point of view. The following two chapters summarize the experimental work on two different bilayer systems. The next chapter deals with the process of contact formation, focal bounding and macroscopic contacts between cells. The cytoskeleton within eucaryotic cells consists of a network of relatively stiff filaments of which three different types of filaments have been identified. As explained in the next chapter much has been recently learned about the interaction of these filaments with the cell membrane. The final two chapters deal with membrane fusion.

W. Fritsche (2001): Mikrobiologie
Type: book by Spektrum Akademischer Verlag.

B. W. Shen, R. Josephs, T. L. Steck (1986): Ultrastructure of the intact skeleton of the human erythrocyte membrane
Type: article by Journal of Cell Biology.
doi: 10.1083/jcb.102.3.997
link: http://jcb.rupress.org/cgi/content/abstract/102/3/997

P. Michaely, D. R. Tomchick, M. Machius, R. G. W. Anderson (2002): Crystal structure of a 12 {ANK} repeat stack from human {ankyrinR}
Type: article by The {EMBO} Journal.
link: http://www.ncbi.nlm.nih.gov/pubmed/12456646
Abstract:

Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. The N-terminal, 'membrane-binding' domain of ankyrins contains 24 {ANK} repeats and mediates most binding activities. Repeats 13-24 are especially active, with known sites of interaction for the {Na/K} {ATPase,} {Cl/HCO(3)} anion exchanger, voltage-gated sodium channel, clathrin heavy chain and L1 family cell adhesion molecules. Here we report the crystal structure of a human {ankyrinR} construct containing {ANK} repeats 13-24 and a portion of the spectrin-binding domain. The {ANK} repeats are observed to form a contiguous spiral stack with which the spectrin-binding domain fragment associates as an extended strand. The structural information has been used to construct models of all 24 repeats of the membrane-binding domain as well as the interactions of the repeats with the {Cl/HCO(3)} anion exchanger and clathrin. These models, together with available binding studies, suggest that ion transporters such as the anion exchanger associate in a large central cavity formed by the {ANK} repeat spiral, while clathrin and cell adhesion molecules associate with specific regions outside this cavity.

E. Sackmann (2006): Thermo-elasticity and adhesion as regulators of cell membrane architecture and function
Type: article by Journal of Physics: Condensed Matter.
link: http://www.iop.org/EJ/abstract/0953-8984/18/45/R02/
Abstract:

Elastic forces and structural phase transitions control the

architecture and function of bio-membranes from the molecular to the microscopic scale of organization. The multi-component lipid bilayer matrix behaves as a pseudo-ternary system. Together with elastically and electrostatically mediated specific lipid-protein interaction mechanisms, fluid-fluid phase separation can occur at physiological temperatures. This can drive the transient generation of micro-domains of distinct composition within multi-component lipid-protein alloys, enabling cells to optimize the efficiency of biochemical reactions by facilitating or inhibiting the access of enzymes by distinct substrates or regulatory proteins. Together with global shape changes governed by the principle of minimum bending energy and induced curvature by macromolecular adsorption, phase separation processes can also play a key role for the sorting of lipids and proteins between intracellular compartments during the vesicle mediated intracellular material transport. Cell adhesion is another example of mechanical force controlled membrane processes. By interplay of attractive lock and key forces, long range disjoining pressures mediated by repeller molecules or membrane undulations and elastic interfacial forces, adhesion induced domain formation can play a dual role for the immunological stimulation of lymphocytes and for the rapid control of the adhesion strength. The present picture of the thermo-elastic control of membrane processes based on concepts of local thermal equilibrium is still rudimentary and has to be extended in the future to account for the intrinsic non-equilibrium situation associated with the constant restructuring of the cellular compartments on a timescale of minutes.

U. Kaupp, K. Koch (1986): Mechanism of photoreception in vertebrate vision
Type: article by Trends in Biochemical Sciences.
doi: 10.1016/0968-0004(86)90232-X
link: https://www.cell.com/trends/biochemical-sciences/abstract/0968-0004(86)90232-X

G. Lee, K. Abdi, Y. Jiang, P. Michaely, V. Bennett, P. E. Marszalek (2006): Nanospring behaviour of ankyrin repeats
Type: article by Nature.
doi: 10.1038/nature04437
link: http://dx.doi.org/10.1038/nature04437

U. Seifert (1997): Configurations of fluid membranes and vesicles
Type: article by Advances in Physics.
link: http://adsabs.harvard.edu/abs/1997AdPhy..46...13S
Abstract:

Vesicles consisting of a bilayer membrane of amphiphilic lipid molecules

are remarkably flexible surfaces that show an amazing variety of shapes of different symmetry and topology. Owing to the fluidity of the membrane, shape transitions such as budding can be induced by temperature changes or the action of optical tweezers. Thermally excited shape fluctuations are both strong and slow enough to be visible by video microscopy. Depending on the physical conditions, vesicles adhere to and unbind from each other or a {substrate.This} article describes the systematic physical theory developed to understand the static and dynamic aspects of membrane and vesicle configurations. The preferred shapes arise from a competition between curvature energy, which derives from the bending elasticity of the membrane, geometrical constraints such as fixed surface area and fixed enclosed volume, and a signature of the bilayer aspect. These shapes of lowest energy are arranged into phase diagrams, which separate regions of different symmetry by continuous or discontinuous transitions. The geometrical constraints affect the fluctuations around these shapes by creating an effective {tension.For} vesicles of non-spherical topology, the conformal invariance of the curvature energy leads to conformal diffusion, which signifies a one-fold degeneracy of the ground state. Unbinding and adhesion transitions arise from the balance between attractive interactions and entropic repulsion or a cost in bending energy, respectively. Both the dynamics of equilibrium fluctuations and the dynamics of shape transformations are governed not only by viscous damping in the surrounding liquid but also by internal friction if the two monolayers slip over each other. More complex membranes such as that of the red blood cell exhibit a variety of new phenomena because of coupling between internal degrees of freedom and external geometry.

J. Kyte, R. F. Doolittle (1982): A simple method for displaying the hydropathic character of a protein
Type: article by Journal of Molecular Biology.
link: http://www.ncbi.nlm.nih.gov/pubmed/7108955

H. Lodish, A. Berk, C. A. Kaiser, M. Krieger, M. P. Scott, A. Bretscher (2007): Molecular Cell Biology
Type: book by Palgrave Macmillan.

S. Manno, Y. Takakuwa, K. Nagao, N. Mohandas (1995): Modulation of Erythrocyte Membrane Mechanical Function by {beta-Spectrin} Phosphorylation and Dephosphorylation
Type: article by Journal of Biological Chemistry.
doi: 10.1074/jbc.270.10.5659
link: http://www.jbc.org/cgi/content/abstract/270/10/5659
Abstract:

The mechanical properties of human erythrocyte membrane are largely regulated by submembranous protein skeleton whose principal components are [alpha]- and [beta]-spectrin, actin, protein 4.1, adducin, and dematin. All of these proteins, except for actin, are phosphorylated by various kinases present in the erythrocyte. In vitro studies with purified skeletal proteins and various kinases has shown that while phosphorylation of these proteins can modify some of the binary and ternary protein interactions, it has no effect on certain other interactions between these proteins. Most importantly, at present there is no direct evidence that phosphorylation of skeletal protein(s) alters the function of the intact membrane. To explore this critical issue, we have developed experimental strategies to determine the functional consequences of phosphorylation of [beta]spectrin on mechanical properties of intact erythrocyte membrane. We have been able to document that membrane mechanical stability is exquisitely regulated by phosphorylation of [beta]-spectrin by membrane-bound casein kinase I. Increased phosphorylation of [beta]-spectrin decreases membrane mechanical stability while decreased phosphorylation increases membrane mechanical stability. Our data for the first time demonstrate that phosphorylation of a skeletal protein in situ can modulate physiological function of native erythrocyte membrane.

R. B. Gennis (1989): Biomembranes. Molecular Structure and Function
Type: book by Springer, Berlin.

R. R. Kopito, H. F. Lodish (1985): Primary structure and transmembrane orientation of the murine anion exchange protein
Type: article by Nature.
doi: 10.1038/316234a0
link: http://dx.doi.org/10.1038/316234a0

G. Wald (1968): Molecular basis of visual excitation
Type: article by Science {(New} York, {N.Y.)}.
link: http://www.ncbi.nlm.nih.gov/pubmed/4877437

V. Gerke, C. E. Creutz, S. E. Moss (2005): Annexins: linking Ca2+ signalling to membrane dynamics
Type: article by Nature Reviews. Molecular Cell Biology.
doi: 10.1038/nrm1661
link: http://www.ncbi.nlm.nih.gov/pubmed/15928709
Abstract:

Eukaryotic cells contain various Ca(2+)-effector proteins that mediate cellular responses to changes in intracellular Ca(2+) levels. A unique class of these proteins - annexins - can bind to certain membrane phospholipids in a Ca(2+)-dependent manner, providing a link between Ca(2+) signalling and membrane functions. By forming networks on the membrane surface, annexins can function as organizers of membrane domains and membrane-recruitment platforms for proteins with which they interact. These and related properties enable annexins to participate in several otherwise unrelated events that range from membrane dynamics to cell differentiation and migration.

R. Beckmann, D. Bubeck, R. Grassucci, P. Penczek, A. Verschoor, G. Blobel, J. Frank (1997): Alignment of Conduits for the Nascent Polypeptide Chain in the {Ribosome-Sec61} Complex
Type: article by Science.
doi: 10.1126/science.278.5346.2123
link: http://www.sciencemag.org/cgi/content/abstract/278/5346/2123

D. N. Wang (1994): Band 3 protein: structure, flexibility and function
Type: article by {FEBS} Letters.
link: http://www.ncbi.nlm.nih.gov/pubmed/8206153
Abstract:

The electroneutral exchange of chloride and bicarbonate across the human erythrocyte membrane is facilitated by Band 3, a 911 amino acid glycoprotein. The 43 {kDa} amino-terminal cytosolic domain binds the cytoskeleton, haemoglobin and glycolytic enzymes. The 52 {kDa} carboxyl-terminal membrane domain mediates anion transport. The protein is a functional dimer, in which the two subunits probably interact with one another by an allosteric mechanism. It is proposed that the link between the mobile cytoplasmic and the membrane-spanning domains of the protein is flexible, based on recent biochemical, biophysical and structural data. This explains the long-standing puzzle that attachment to the cytoskeletal spectrin and actin does not appear to restrict the rotational movement of the Band 3 protein in the erythrocyte membrane. In the Band 3 isoform from the Southeast Asian Ovalocytes {(SAO)} this link is altered, resulting a tighter attachment of the cytoskeleton to the plasma membrane and a more rigid red blood cell.

P. F. Devaux (1988): Phospholipid flippases
Type: article by {FEBS} Letters.
link: http://www.ncbi.nlm.nih.gov/pubmed/3292284
Abstract:

Protein mediated phospholipid translocation through membranes has been observed in rat liver endoplasmic reticulum and in the plasma membrane of erythrocytes as well as in a few other cell membranes. Lipid translocation in plasma membranes is {ATP} dependent and selectively accumulates aminophospholipids on the inner monolayers.

K. Palczewski, T. Kumasaka, T. Hori, C. A. Behnke, H. Motoshima, B. A. Fox, I. Le Trong, D. C. Teller, T. Okada, R. E. Stenkamp, M. Yamamoto, M. Miyano (2000): Crystal Structure of Rhodopsin: A G {Protein-Coupled} Receptor
Type: article by Science.
doi: 10.1126/science.289.5480.739
link: http://www.sciencemag.org/cgi/content/abstract/289/5480/739

G. A. Jamieson (1977): Mammalian Cell Membranes: Volume Two: The Diversity of Membranes
Type: book by {Butterworth-Heinemann} Ltd.

J. M. Berg, L. Stryer, J. L. Tymoczko (2007): Biochemie
Type: book by Spektrum Akademischer Verlag.

V. Bennett (2005): {Spectrin-Based} Membrane Skeleton: A Multipotential Adaptor Between Plasma Membrane and Cytoplasm
Type: article by Physiological Reviews.
link: http://physrev.physiology.org/cgi/content/abstract/71/1/330-r
Abstract:

Pages 1029-1065: Vann Bennett. {"Spectrin-Based} Membrane Skeleton: A Multipotential Adaptor Between Plasma Membrane and Cytoplasm." Page 1056: Ref. 36 should read {BENNETT,} H., and J. {CONDEELIS.} Isolation of an immunoreactive analogue of brain fodrin that is associated with the cell cortex of Dictyostelium amoebae. Cell Motil. Cytoskeleton 11: 303-317, 1988.

W. R. Bishop, R. M. Bell (1988): Assembly of phospholipids into cellular membranes: biosynthesis, transmembrane movement and intracellular translocation
Type: article by Annual Review of Cell Biology.
doi: 10.1146/annurev.cb.04.110188.003051
link: http://www.ncbi.nlm.nih.gov/pubmed/3058167

E. Ritter, K. Zimmermann, M. Heck, K. P. Hofmann, F. J. Bartl (2004): Transition of rhodopsin into the active metarhodopsin {II} state opens a new light-induced pathway linked to Schiff base isomerization
Type: article by The Journal of Biological Chemistry.
doi: 10.1074/jbc.M406857200
link: http://www.ncbi.nlm.nih.gov/pubmed/15322129
Abstract:

Rhodopsin bears 11-cis-retinal covalently bound by a protonated Schiff base linkage. 11-cis/all-trans isomerization, induced by absorption of green light, leads to active metarhodopsin {II,} in which the Schiff base is intact but deprotonated. The subsequent metabolic retinoid cycle starts with Schiff base hydrolysis and release of photolyzed all-trans-retinal from the active site and ends with the uptake of fresh 11-cis-retinal. To probe chromophore-protein interaction in the active state, we have studied the effects of blue light absorption on metarhodopsin {II} using infrared and time-resolved {UV-visible} spectroscopy. A light-induced shortcut of the retinoid cycle, as it occurs in other retinal proteins, is not observed. The predominantly formed illumination product contains all-trans-retinal, although the spectra reflect Schiff base reprotonation and protein deactivation. By its kinetics of formation and decay, its low temperature photointermediates, and its interaction with transducin, this illumination product is identified as metarhodopsin {III.} This species is known to bind all-trans-retinal via a reprotonated Schiff base and forms normally in parallel to retinal release. We find that its generation by light absorption is only achieved when starting from active metarhodopsin {II} and is not found with any of its precursors, including metarhodopsin I. Based on the finding of others that metarhodopsin {III} binds retinal in {all-trans-C(15)-syn} configuration, we can now conclude that light-induced formation of metarhodopsin {III} operates by Schiff base isomerization ("second switch"). Our reaction model assumes steric hindrance of the retinal polyene chain in the active conformation, thus preventing central double bond isomerization.

M. J. F. Broderick, S. J. Winder (2002): Towards a complete atomic structure of spectrin family proteins
Type: article by Journal of Structural Biology.
doi: 10.1006/jsbi.2002.4465
link: http://www.ncbi.nlm.nih.gov/pubmed/12064945
Abstract:

The spectrin family of proteins represents a discrete group of cytoskeletal proteins comprising principally alpha-actinin, spectrin, dystrophin, and homologues and isoforms. They all share three main structural and functional motifs, namely, the spectrin repeat, {EF-hands,} and a {CH} domain-containing actin-binding domain. These proteins are variously involved in organisation of the actin cytoskeleton, membrane cytoskeleton architecture, cell adhesion, and contractile apparatus. The highly modular nature of these molecules has been a hindrance to the determination of their complete structures due to the inherent flexibility imparted on the proteins, but has also been an asset, inasmuch as the individual modules were of a size amenable to structural analysis by both crystallographic and {NMR} approaches. Representative structures of all the major domains shared by spectrin family proteins have now been solved at atomic resolution, including in some cases multiple domains from several family members. High-resolution structures, coupled with lower resolution methods to determine the overall molecular shape of these proteins, allow us for the first time to build complete atomic structures of the spectrin family of proteins.

R. F. Schmidt, G. Thews, F. Lang (2000): Physiologie des Menschen
Type: book by Springer Berlin.

S. C. Liu, L. H. Derick, J. Palek (1987): Visualization of the hexagonal lattice in the erythrocyte membrane skeleton
Type: article by Journal of Cell Biology.
doi: 10.1083/jcb.104.3.527
link: http://jcb.rupress.org/cgi/content/abstract/104/3/527

Kapitel 10

M. Tanaka, E. Sackmann (2005): Polymer-supported membranes as models of the cell surface
Type: article by Nature.
doi: 10.1038/nature04164
link: http://dx.doi.org/10.1038/nature04164

P. F. F. Almeida, W. L. C. Vaz (1995): Lateral Diffusion in Membranes
Type: book by Elsevier Science, Amsterdam.

E. Evans, D. Needham (1987): Physical properties of surfactant bilayer membranes: thermal transitions, elasticity, rigidity, cohesion and colloidal interactions
Type: article by The Journal of Physical Chemistry.
doi: 10.1021/j100300a003
link: http://dx.doi.org/10.1021/j100300a003

P. C. Hiemenz, R. Rajagopalan (1997): Principles of Colloid and Surface Chemistry
Type: book by Marcel Dekker Inc.

M. Tomishige, A. Kusumi (1999): Compartmentalization of the Erythrocyte Membrane by the Membrane Skeleton: Intercompartmental Hop Diffusion of Band 3
Type: article by Molecular Biology of the Cell.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=25476

J. Seelig (1977): Deuterium magnetic resonance: theory and application to lipid membranes
Type: article by Quarterly Reviews of Biophysics.
link: http://www.ncbi.nlm.nih.gov/pubmed/335428

H. H. Mantsch, R. N. McElhaney (1991): Phospholipid phase transitions in model and biological membranes as studied by infrared spectroscopy
Type: article by Chemistry and Physics of Lipids.
link: http://www.ncbi.nlm.nih.gov/pubmed/2054905
Abstract:

Fourier transform infrared {(FT-IR)} spectroscopy is an extremely powerful yet non-perturbing physical technique for monitoring the conformation and dynamics of all portions of the phospholipid molecule. In this brief review we summarize some recent {FT-IR} spectroscopic studies of phospholipid phase transitions in model lipid bilayer and in biological membranes which illustrate the great utility of this technique. We show that {FT-IR} spectroscopy can accurately monitor the gel to liquid-crystalline phase transition and can provide a large amount of detailed information about phospholipid structure and organization in both the gel and liquid-crystalline states of lipid bilayers.

J. H. Ipsen, O. G. Mouritsen, M. J. Zuckermann (1989): Theory of thermal anomalies in the specific heat of lipid bilayers containing cholesterol.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1280522&rendertype=abstract

H. Heller, M. Schaefer, K. Schulten (1993): Molecular dynamics simulation of a bilayer of 200 lipids in the gel and in the liquid crystal phase
Type: article by The Journal of Physical Chemistry.
doi: 10.1021/j100133a034
link: http://dx.doi.org/10.1021/j100133a034

J. N. Israelachvili (1991): Intermolecular and Surface Forces: With Applications to Colloidal and Biological Systems
Type: book by Academic Pr Inc.

L. D. Landau, E. M. Lifschitz (1991): Lehrbuch der theoretischen Physik, 10 Bde., Bd.7, Elastizitätstheorie: {BD} 7
Type: book by Deutsch {(Harri)}.

E. Sackmann (2006): Thermo-elasticity and adhesion as regulators of cell membrane architecture and function
Type: article by Journal of Physics: Condensed Matter.
link: http://www.iop.org/EJ/abstract/0953-8984/18/45/R02/
Abstract:

Elastic forces and structural phase transitions control the

architecture and function of bio-membranes from the molecular to the microscopic scale of organization. The multi-component lipid bilayer matrix behaves as a pseudo-ternary system. Together with elastically and electrostatically mediated specific lipid-protein interaction mechanisms, fluid-fluid phase separation can occur at physiological temperatures. This can drive the transient generation of micro-domains of distinct composition within multi-component lipid-protein alloys, enabling cells to optimize the efficiency of biochemical reactions by facilitating or inhibiting the access of enzymes by distinct substrates or regulatory proteins. Together with global shape changes governed by the principle of minimum bending energy and induced curvature by macromolecular adsorption, phase separation processes can also play a key role for the sorting of lipids and proteins between intracellular compartments during the vesicle mediated intracellular material transport. Cell adhesion is another example of mechanical force controlled membrane processes. By interplay of attractive lock and key forces, long range disjoining pressures mediated by repeller molecules or membrane undulations and elastic interfacial forces, adhesion induced domain formation can play a dual role for the immunological stimulation of lymphocytes and for the rapid control of the adhesion strength. The present picture of the thermo-elastic control of membrane processes based on concepts of local thermal equilibrium is still rudimentary and has to be extended in the future to account for the intrinsic non-equilibrium situation associated with the constant restructuring of the cellular compartments on a timescale of minutes.

H. Träuble (1971): The movement of molecules across lipid membranes: A molecular theory
Type: article by Journal of Membrane Biology.
doi: 10.1007/BF02431971
link: http://dx.doi.org/10.1007/BF02431971
Abstract:

Summary The movement of molecules across membranes is discussed in terms of thermal fluctuations in the hydrocarbon chains of the

membrane lipids. The thermal motion of the hydrocarbon chains results in the formation of conformational isomers, so-called kink-isomers of the hydrocarbon chains. {“Kinks”} may be pictured as mobile structural defects which represent small, mobile free volumes in the hydrocarbon phase of the membrane. The diffusion coefficient of kinks is calculated to be 10−5 cm2/sec; thus kinks diffusion is a fast process. Small molecules can enter into the free volumes of kinks and migrate across the membrane together with the kinks; thus kinks may be regarded as intrinsic carriers of lipid membranes. An expression is derived from this model for the flow of molecules through lipid membranes. The calculated value for the water permeability is compatible with measurements on lipid bilayers.

G. Buldt, H. U. Gally, A. Seelig, J. Seelig, G. ZACCAI (1978): Neutron diffraction studies on selectively deuterated phospholipid bilayers
Type: article by Nature.
doi: 10.1038/271182a0
link: http://dx.doi.org/10.1038/271182a0

A. Ben-Shaul Molecular theory of chain packing, elasticity and lipid-protein interaction in lipid bilayers
Type: article

P. G. Saffman, M. Delbrück (1975): Brownian motion in biological membranes
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
doi: VL - 72
link: http://www.pnas.org/content/72/8/3111.abstract
Abstract:

Brownian motion (diffusion) of particles in membranes occurs in a highly anisotropic environment. For such particles a translational mobility (independent of velocity) can be defined if the viscosity of the liquid embedding the membrane is taken into account. The results of a model calculation are presented. They suggest that for a realistic situation translational diffusion should be about four times faster in relation to rotational diffusion than in the isotropic case.

O. Albrecht, H. Gruler, E. Sackmann (1978): Polymorphism of phospholipid monolayers
Type: article by Journal de Physique.
doi: 10.1051/jphys:01978003903030100

S. T. Hess, S. Huang, A. A. Heikal, W. W. Webb (2002): Biological and Chemical Applications of Fluorescence Correlation Spectroscopy: A Review†
Type: article by Biochemistry.
doi: 10.1021/bi0118512
link: http://dx.doi.org/10.1021/bi0118512

P. Schwille, E. Haustein (2001): Fluorescence Correlation Spectroscopy
Type: book
Abstract:

The recent development of single molecule detection techniques has opened new horizons for the study of individual macromolecules under physiological conditions. Conformational subpopulations, internal dynamics and activity of single biomolecules, parameters that have so far been hidden in large ensemble averages, are now being unveiled. Herein, we review a particular attractive solution-based single molecule technique, fluorescence correlation spectroscopy {(FCS).} This time-averaging fluctuation analysis which is usually performed in Confocal setups combines maximum sensitivity with high statistical confidence. {FCS} has proven to be a very versatile and powerful tool for detection and temporal investigation of biomolecules at ultralow concentrations on surfaces, in solution, and in living cells. The introduction of dual-color cross-correlation and two-photon excitation in {FCS} experiments is currently increasing the number of promising applications of {FCS} to biological research.

S. König, W. Pfeiffer, T. Bayerl, D. Richter, E. Sackmann (1992): Molecular dynamics of lipid bilayers studied by incoherent quasi-elastic neutron scattering
Type: article by Journal de Physique {II}.
doi: 10.1051/jp2:1992100

H. E. Stanley (1971): Introduction to Phase Transitions and Critical Phenomena
Type: book by {Oxf.U.P.}.

O. G. Mouritsen, M. Bloom (1984): Mattress model of lipid-protein interactions in membranes.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1435039&rendertype=abstract

E. Evans, E. Sackmann (1988): Translational and Rotational Drag Coefficients for a Disk Moving in a Liquid Membrane Associated with a Rigid Substrate
Type: article by Journal of Fluid Mechanics Digital Archive.
doi: 10.1017/S0022112088003106
link: http://journals.cambridge.org/action/displayAbstract;jsessionid=D698D6F9D374DDAE983E12893A26D888.tomcat1?fromPage=online&aid=394801

L. D. Landau, E. M. Lifschitz (1991): Lehrbuch der theoretischen Physik, 10 Bde., Bd.6, Hydrodynamik: {BD} 6
Type: book by Deutsch {(Harri)}.

J. Rika, T. Binkert (1989): Direct measurement of a distinct correlation function by fluorescence cross correlation
Type: article by Physical Review A..
link: http://www.ncbi.nlm.nih.gov/pubmed/9901536

G. J. Schütz, G. Kada, V. P. Pastushenko, H. Schindler (2000): Properties of lipid microdomains in a muscle cell membrane visualized by single molecule microscopy
Type: article by The {EMBO} Journal.
doi: 10.1093/emboj/19.5.892
link: http://www.ncbi.nlm.nih.gov/pubmed/10698931
Abstract:

The lateral motion of single fluorescence labeled lipid molecules was imaged in native cell membranes on a millisecond time scale and with positional accuracy of approximately 50 nm, using 'single dye tracing'. This first application of single molecule microscopy to living cells rendered possible the direct observation of lipid-specific membrane domains. These domains were sensed by a lipid probe with saturated acyl chains as small areas in a liquid-ordered phase: the probe showed confined but fast diffusion, with high partitioning (approximately 100-fold) and long residence time (approximately 13 s). The analogous probe with mono-unsaturated chains diffused predominantly unconfined within the membrane. With approximately 15 saturated probes per domain, the locations, sizes, shapes and motions of individual domains became clearly visible. Domains had a size of 0.7 micrometer (0.2-2 micrometer), covering approximately 13% of total membrane area. Both the liquid-ordered phase characteristics and the sizes of domains match properties of membrane fractions described as detergent-resistant membranes {(DRMs),} strongly suggesting that the domains seen are the in vivo correlate of {DRMs} and thus may be identified as lipid rafts.

J. M. Seddon, R. H. Templer (1995): Polymorphism of {Lipid-Water} Systems in Structure and Dynamics of Membranes. From Cells to Vesicles
Type: article by Structure and Dynamics of Membranes, Generic and Specific Interaction, Handbook of Biological Physics, Elsevier, Amsterdam.

G. Breton, J. Danyluk, F. Ouellet, F. Sarhan (2000): Biotechnological applications of plant freezing associated proteins
Type: article by Biotechnology Annual Review.
link: http://www.ncbi.nlm.nih.gov/pubmed/11193297
Abstract:

Plants use a wide array of proteins to protect themselves against low temperature and freezing conditions. The identification of these freezing tolerance associated proteins and the elucidation of their cryoprotective functions will have important applications in several fields. Genes encoding structural proteins, osmolyte producing enzymes, oxidative stress scavenging enzymes, lipid desaturases and gene regulators have been used to produce transgenic plants. These studies have revealed the potential capacity of different genes to protect against temperature related stresses. In some cases, transgenic plants with significant cold tolerance have been produced. Furthermore, the biochemical characterization of the cold induced antifreeze proteins and dehydrins reveals many applications in the food and the medical industries. These proteins are being considered as food additives to improve the quality and shelf-life of frozen foods, as cryoprotective agents for organ and cell cryopreservation, and as chemical adjuvant in cancer cryosurgery.

M. Bee (1988): Quasielastic Neutron Scattering: Principles and Applications in Solid State Chemistry, Biology and Materials Science
Type: book by Institute of Physics Publishing.

D. Axelrod, D. E. Koppel, J. Schlessinger, E. Elson, W. W. Webb (1976): Mobility measurement by analysis of fluorescence photobleaching recovery kinetics.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1334945&rendertype=abstract

H. Möhwald (1996): Phospholipid Monolayers
Type: article by Handbook of Biological Physics, Elsevier.

H. J. Galla, W. Hartmann, U. Theilen, E. Sackmann (1979): On two-dimensional passive random walk in lipid bilayers and fluid pathways in biomembranes
Type: article by The Journal of Membrane Biology.
link: http://www.ncbi.nlm.nih.gov/pubmed/40032
Abstract:

The lateral mobility of pyrene, pyrene decanoic acid, and 1-palmitoyl-2-pyrene decanoyl-phosphatidyl choline (pyrene lecithin) in lipid bilayers is determined by the excimer formation technique. This method is applied to vesicles of lecithins differing in chain length and in the degree of saturation of the hydrocarbon chains. These values are compared with results in cephalins of different chain length and in dipalmitoyl phosphatidic acid at variable {pH.} The influence of cholesterol is investigated. The results are analyzed in terms of the Montroll model of two-dimensional random walk. The jump frequency of the probe molecule within the lipid lattice is obtained. The advantage of this measure of transport in lipid layers is that it does not involve lipid lattice parameters. The main results of the present work are: (i) The lateral mobility of a given solute molecule in lamellae of saturated lecithins is independent of hydrocarbon chain length and rather a universal function of temperature. (ii) In unsaturated dioleyl lecithin the amphiphatic molecules have lateral mobilities of the same size as in saturated lipids. The jump frequency of pyrene, however, is by a factor of two larger in the unsaturated lecithin. (iii) The jump frequencies in phosphatidyl ethanolamines are about equal to those in lecithins. (iv) In phosphatidic acid layers the hopping frequencies depend on the charges of the head groups of both the lipids and the probes. (v) Cholesterol strongly reduces the jump frequency in fluid layers. (vi) The lateral mobility in biological membranes is comparable to that in artificial lipid bilayers. The experimental results are discussed in terms of the free volume model of diffusion in fluids. Good agreement with the predictions made from this model is found. A striking result is the observation of a tilt in dioleyl-lecithin bilayer membranes from the hopping frequencies of pyrene and pyrene lecithin. A tilt angle of phi = 17 degrees is estimated.

C. Tanford (1980): The Hydrophobic Effect: Formation of Micelles and Biological Membranes
Type: book by John Wiley & Sons Inc.

T. Köchy, T. M. Bayerl (1993): Lateral diffusion coefficients of phospholipids in spherical bilayers on a solid support measured by {2H-nuclear-magnetic-resonance} relaxation
Type: article by Physical Review. E, Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics.
link: http://www.ncbi.nlm.nih.gov/pubmed/9960231

C. Gliss, O. Randel, H. Casalta, E. Sackmann, R. Zorn, T. Bayerl (1999): Anisotropic motion of cholesterol in oriented {DPPC} bilayers studied by quasielastic neutron scattering: the liquid-ordered phase.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1300333&rendertype=abstract

J. F. Nagle, R. Zhang, S. Tristram-Nagle, W. Sun, H. I. Petrache, R. M. Suter (1996): X-ray structure determination of fully hydrated L alpha phase dipalmitoylphosphatidylcholine bilayers.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1225068&rendertype=abstract

K. Tu, M. L. Klein, D. J. Tobias (1998): Constant-pressure molecular dynamics investigation of cholesterol effects in a dipalmitoylphosphatidylcholine bilayer.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1299887&rendertype=abstract

L. Saiz, M. L. Klein (2002): Computer simulation studies of model biological membranes
Type: article by Accounts of chemical research.

G. Büldt, H. U. Gally, J. Seelig, G. Zaccai (1979): Neutron diffraction studies on phosphatidylcholine model membranes. I. Head group conformation
Type: article by Journal of Molecular Biology.
link: http://www.ncbi.nlm.nih.gov/pubmed/537074

M. Bloom, E. Evans, O. G. Mouritsen (1991): Physical properties of the fluid lipid-bilayer component of cell membranes: a perspective
Type: article by Quarterly Reviews of Biophysics.
link: http://www.ncbi.nlm.nih.gov/pubmed/1749824

J. H. Ipsen, O. G. Mouritsen, M. Bloom (1990): Relationships between lipid membrane area, hydrophobic thickness, and acyl-chain orientational order. The effects of cholesterol.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1280735&rendertype=abstract

F. Jähnig (1976): Electrostatic free energy and shift of the phase transition for charged lipid membranes
Type: article by Biophysical Chemistry.
link: http://www.ncbi.nlm.nih.gov/pubmed/953150
Abstract:

For a charged membrane in an electrolyte solution the electrostatic free energy is derived treating the system as a diffuse double layer. The dependence of the energy on external parameters like surface charge density and temperature is obtained and the physical basis discussed. As an application the charges are shown to exert an electrostatic surface pressure on the lipid chain packing which leads to a shift in the phase transition of membranes. The results confirm the interpretation of experimental data as given by Träuble et al. in the accompanying paper.

K. Mortensen, W. Pfeiffer, E. Sackmann, W. Knoll (1988): Structural properties of a phosphatidylcholine-cholesterol system as studied by small-angle neutron scattering: ripple structure and phase diagram
Type: article by Biochimica Et Biophysica Acta.
link: http://www.ncbi.nlm.nih.gov/pubmed/3191122
Abstract:

Small-angle neutron scattering has been used to study structural features of lamellar bilayer membranes of dimyristoylphosphatidylcholine {(DMPC)} and {DMPC} mixed with various amount of cholesterol. The studies were recorded at a fixed hydration level of 17% {2H2O,} i.e. just below saturation. Bragg reflections gives information on the ripple structure and on the bilayer periodicity. The crystalline Lc phase, which was stabilized after long time storage at low temperature, exhibits major small angle scattering when cholesterol is mixed into the membrane. The intermediate P beta' gel-phase, which is characteristic by the rippled structure, is dramatically stabilized by the introduction of cholesterol. The ripple structure depends significantly both on the cholesterol content and on the temperature. At high temperatures, T greater than 15 degrees C, the inverse ripple periodicity varies basically linearly with cholesterol content, and approach zero (i.e. periodicity goes to infinite) at 20 mol% cholesterol, approximately. At lower temperatures the correlation is more complex. The data indicate additional phase boundaries below 2 mol% and at approx. 8 mol%. Secondary rippled structures are observed in the low temperature L beta'-phase for cholesterol content below approx. 8 mol%. The data gives detailed insight into the phosphatidylcholine cholesterol phase diagram, which is discussed on the basis of a simple model in which the cholesterol complexes are fixed to the defect stripes of the rippled structure.

A. Tardieu, V. Luzzati, F. C. Reman (1973): Structure and polymorphism of the hydrocarbon chains of lipids: a study of lecithin-water phases
Type: article by Journal of Molecular Biology.
link: http://www.ncbi.nlm.nih.gov/pubmed/4738730

E. Evans, F. Ludwig (2000): Dynamic strengths of molecular anchoring and material cohesion in fluid biomembranes
Type: article by Journal of Physics Condensed Matter.
link: http://adsabs.harvard.edu/abs/2000JPCM...12..315E
Abstract:

Building on Kramers' theory for reaction kinetics in liquids and using

laboratory experiments, we show how strengths of molecular anchoring and material cohesion in fluid-lipid membranes increase with rate of force and tension loading. Expressed on a scale of log(loading rate), the dynamic spectra of pull-out forces and rupture tensions image the microscopic and mesoscopic energy barriers traversed in molecular extraction and membrane failure. To capture such images, we have pulled single molecules from membranes with force rates from 1 to 104 {pN} s-1 and ruptured giant membrane vesicles with tension rates from 10-2 to 102 {mN} m-1 s-1 .

D. Turnbull, M. H. Cohen (1961): {Free-Volume} Model of the Amorphous Phase: Glass Transition
Type: article by The Journal of Chemical Physics.
doi: 10.1063/1.1731549
link: http://link.aip.org/link/?JCP/34/120/1
Abstract:

Free volume vf is defined as that part of the thermal expansion, or excess volume Deltav-bar which can be redistributed without energy change. Assuming a {Lennard-Jones} potential function for a molecule within its cage in the condensed phase, it can be shown that at small Deltav-bar considerable energy is required to redistribute the excess volume; however, at Deltav-bar considerably greater than some value deltav-bar g (corresponding to potentials within the linear region), most of the volume added can be redistributed freely. The transition from glass to liquid may be associated with the introduction of appreciable free volume into the system. Free volume will be distributed at random within the amorphous phase and there is a contribution to the entropy from this randomness which is not present in the entropy of the crystalline phase. According to our model all liquids would become glasses at sufficiently low temperature if crystallization did not intervene. Therefore whether or not a glass forms is determined by the crystallization kinetic constants and the cooling rate of the liquid. The experience on the glass formation is consistent with the generalization: at a given level of cohesive energy the glass-forming tendency of a substance in a particular class is greater the less is the ratio of the energy to the entropy of crystallization.

M. A. Medina, P. Schwille (2002): Fluorescence correlation spectroscopy for the detection and study of single molecules in biology
Type: article by {BioEssays}.
doi: 10.1002/bies.10118
link: http://dx.doi.org/10.1002/bies.10118
Abstract:

The recent development of single molecule detection techniques has opened new horizons for the study of individual macromolecules under physiological conditions. Conformational subpopulations, internal dynamics and activity of single biomolecules, parameters that have so far been hidden in large ensemble averages, are now being unveiled. Herein, we review a particular attractive solution-based single molecule technique, fluorescence correlation spectroscopy {(FCS).} This time-averaging fluctuation analysis which is usually performed in Confocal setups combines maximum sensitivity with high statistical confidence. {FCS} has proven to be a very versatile and powerful tool for detection and temporal investigation of biomolecules at ultralow concentrations on surfaces, in solution, and in living cells. The introduction of dual-color cross-correlation and two-photon excitation in {FCS} experiments is currently increasing the number of promising applications of {FCS} to biological research. {BioEssays} 24:758-764, 2002. © 2002 Wiley Periodicals, Inc.

L. van Hove (1954): Temperature Variation of the Magnetic Inelastic Scattering of Slow Neutrons
Type: article by Physical Review.
doi: 10.1103/PhysRev.93.268
link: http://link.aps.org/abstract/PR/v93/p268
Abstract:

The main features of the temperature variation of the magnetic inelastic scattering of slow neutrons in iron, recently measured by Palevsky and Hughes, are accounted for, by use of a theoretical description of the scattering in terms of the correlation between pairs of spins at different positions and different times. Proofs will be given in a later paper devoted to a general discussion of space-time correlations and of their use in scattering theory.

Kapitel 11

A. Zilker, M. Ziegler, E. Sackmann (1992): Spectral analysis of erythrocyte flickering in the 0.34-mum-1 regime by microinterferometry combined with fast image processing
Type: article by Physical Review A.
doi: 10.1103/PhysRevA.46.7998
link: http://link.aps.org/abstract/PRA/v46/p7998
Abstract:

Reflection interference microscopy in combination with real-time image processing was applied to determine the spatial spectrum of the mean-square amplitude of erythrocyte flickering in the wave-vector regime 0.3≤q≤4 μm-1. The mean-square amplitude scales as q4±ε for q≥0.7 μm-1, suggesting that flickering is dominated mainly by bending stiffness. We measured a bending modulus of Kc=(2±0.5)×10-20 N m as compared to Kc=(5±1.5)×10-20 N m found for dimyristoylphosphatidylcholine {(DMPC)} vesicles with the same technique.

T. Auth, S. A. Safran, N. S. Gov (2007): Fluctuations of coupled fluid and solid membranes with application to red blood cells
Type: article by Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics.
link: http://www.ncbi.nlm.nih.gov/pubmed/18233690
Abstract:

The fluctuation spectra and the intermembrane interaction of two membranes at a fixed average distance are investigated. Each membrane can either be a fluid or a solid membrane, and in isolation, its fluctuations are described by a bare or a wave-vector-dependent bending modulus, respectively. The membranes interact via their excluded-volume interaction; the average distance is maintained by an external, homogeneous pressure. For strong coupling, the fluctuations can be described by a single, effective membrane that combines the elastic properties. For weak coupling, the fluctuations of the individual, noninteracting membranes are recovered. The case of a composite membrane consisting of one fluid and one solid membrane can serve as a microscopic model for the plasma membrane and cytoskeleton of the red blood cell. We find that, despite the complex microstructure of bilayers and cytoskeletons in a real cell, the fluctuations with wavelengths lambda greater, similar 400 nm are well described by the fluctuations of a single, polymerized membrane (provided that there are no inhomogeneities of the microstructure). The model is applied to the fluctuation data of discocytes ("normal" red blood cells), a stomatocyte, and an echinocyte. The elastic parameters of the membrane and an effective temperature that quantifies active, metabolically driven fluctuations are extracted from the experiments.

E. A. Evans (1974): Bending Resistance and Chemically Induced Moments in Membrane Bilayers
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1334588&rendertype=abstract

R. Cahn, W. Ludwig (1985): Theorie der Wärme.
Type: book by Springer, Berlin.

Y. C. Fung (1993): Biomechanics. Mechanical Properties of Living Tissues
Type: book by {Springer-Verlag} {GmbH}.

R. W. Cahn, P. Haasen (1996): Physical Metallurgy, Revised and Enhanced Edition 3 Volume Set
Type: book by Elsevier Science & Technology.

Mark A. Peterson (1992): Linear response of the human erythrocyte to mechanical stress
Type: article by Physical Review A.
doi: 10.1103/PhysRevA.45.4116
link: http://link.aps.org/abstract/PRA/v45/p4116
Abstract:

The human erythrocyte readily changes its shape in response to mechanical stress. Geometrical methods are used to analyze this effect in three experiments: thermal shape fluctuation (flicker), electrodeformation, and tank treading, which is the circulation of the membrane around the interior fluid in a shear flow. Comparison with existing data indicates that both flicker and tank treading represent the motion of a fluid membrane. At the same time it is a solid membrane (i.e., possessing a shear modulus) that resists large-scale shape change. This combination of fluid and solid membrane properties is in some ways paradoxical.

S. Svetina, B. Zeks (1989): Membrane bending energy and shape determination of phospholipid vesicles and red blood cells
Type: article by European Biophysics Journal: {EBJ}.
link: http://www.ncbi.nlm.nih.gov/pubmed/2766997
Abstract:

A procedure is developed to calculate red blood cell and phospholipid vesicle shapes within the bilayer couple model of the membrane. The membrane is assumed to consist of two laterally incompressible leaflets which are in close contact but unconnected. Shapes are determined by minimizing the membrane bending energy at a given volume of a cell {(V),} given average membrane area {(A)} and given difference of the areas of two leaflets (delta A). Different classes of shapes exist in parts of the v/delta a phase diagram, where v and delta a are the volume and the leaflet area difference relative to the sphere with area A. The limiting shapes are composed of sections of spheres with only two values allowed for their radii. Two low energy axisymmetrical classes, which include discocyte and stomatocyte shapes are studied and their phase diagrams are analyzed. For v= 0.6, the discocyte is the lowest energy shape, which transforms by decreasing delta a continuously into a stomatocyte. The spontaneous membrane curvature {(C0)} and compressibility of membrane leaflets can be incorporated into the model. A model, where delta A is free and C0 determines the shapes at given V and A, is also studied. In this case, by decreasing C0, a discocyte transforms discontinuously into an almost closed stomatocyte.

H. P. Duwe, E. Sackmann (1990): Bending elasticity and thermal excitations of lipid bilayer vesicles: Modulation by solutes
Type: article by Physica A Statistical Mechanics and its Applications.
link: http://adsabs.harvard.edu/abs/1990PhyA..163..410D
Abstract:

We present high-precision measurements of the bending elastic moduli of

bilayers of a variety of different lipids and of modifications of the flexural rigidity by solutes. The measurements are based on the Fourier analysis of thermally excited membrane undulations (vesicle shape fluctuations) using a recently developed dynamic image processing method. Measurements of the bending modulus as a function of the undulation wave vector provide information on the limitation of the excitations by the constraint of finite membrane area (surface tension effects) and by transient lateral tensions arising in each monolayer by restricted diffusion at high wave vectors. Measurements of the autocorrelation function of the undulation amplitudes provide a further test of the theoretical models. Studies of the effect of solutes show that cholesterol increases the bending modulus of dimyristoylphosphatidylcholine from Kc = 1. 1 � 10-12 erg to 4.2 � 10-12 erg (at 30 mol%). Incorporation of a short bipolar lipid reduces Kc to the order of {kT.} Finally we present a variety of shape changes of vesicle and provide evidence for the stabilization of metastable non-equilibrium shapes by lateral phase separation.

H.-G. Döbereiner, E. Evans, M. Kraus, U. Seifert, M. Wortis (1997): Mapping vesicle shapes into the phase diagram: A comparison of experiment and theory
Type: article by Physical Review E.
doi: 10.1103/PhysRevE.55.4458
link: http://link.aps.org/abstract/PRE/v55/p4458
Abstract:

Phase-contrast microscopy is used to monitor the shapes of micron-scale fluid-phase phospholipid-bilayer vesicles in an aqueous solution. At fixed temperature, each vesicle undergoes thermal shape fluctuations. We are able, experimentally, to characterize the thermal shape ensemble by digitizing the vesicle outline in real time and storing the time sequence of images. Analysis of this ensemble using the area-difference-elasticity {(ADE)} model of vesicle shapes allows us to associate (map) each time sequence to a point in the zero-temperature (shape) phase diagram. Changing the laboratory temperature modifies the control parameters (area, volume, etc.) of each vesicle, so it sweeps out a trajectory across the theoretical phase diagram. It is a nontrivial test of the {ADE} model to check that these trajectories remain confined to regions of the phase diagram where the corresponding shapes are locally stable. In particular, we study the thermal trajectories of three prolate vesicles which, upon heating, experienced a mechanical instability leading to budding. We verify that the position of the observed instability and the geometry of the budded shape are in reasonable accord with the theoretical predictions. The inability of previous experiments to detect the ``hidden control parameters (relaxed area difference and spontaneous curvature) make this the first direct quantitative confrontation between vesicle-shape theory and experiment.

L. D. Landau, E. M. Lifschitz (1991): Lehrbuch der theoretischen Physik, 10 Bde., Bd.7, Elastizitätstheorie: {BD} 7
Type: book by Deutsch {(Harri)}.

R. Mukhopadhyay, G. Lim H W, M. Wortis (2002): Echinocyte shapes: bending, stretching, and shear determine spicule shape and spacing
Type: article by Biophysical Journal.
link: http://www.ncbi.nlm.nih.gov/pubmed/11916836
Abstract:

We study the shapes of human red blood cells using continuum mechanics. In particular, we model the crenated, echinocytic shapes and show how they may arise from a competition between the bending energy of the plasma membrane and the stretching/shear elastic energies of the membrane skeleton. In contrast to earlier work, we calculate spicule shapes exactly by solving the equations of continuum mechanics subject to appropriate boundary conditions. A simple scaling analysis of this competition reveals an elastic length Lambda(el), which sets the length scale for the spicules and is, thus, related to the number of spicules experimentally observed on the fully developed echinocyte.

J. Käs, E. Sackmann (1991): Shape transitions and shape stability of giant phospholipid vesicles in pure water induced by area-to-volume changes
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(91)82117-8
link: http://www.ncbi.nlm.nih.gov/pubmed/1742455
Abstract:

Shape transformations of vesicles of dimyristoylphosphatidylcholine (= {DMPC)} and palmitoyloleylphosphatidylcholine (= {POPC)} in ion-free water were induced by changing the area-to-volume ratio via temperature variations. Depending on the pretreatment we find several types of shape changes for {DMPC} (in pure water) at increasing area-to-volume ratio: (a) budding transitions leading to the formation of a chain of vesicles at further increase of the area-to-volume ratio, (b) discocyte-stomatocyte transitions, (c) reentrant dumbbell-pear-dumbbell transitions, and (d) spontaneous blebbing and/or tether formation of spherical vesicles. Beside these transitions a more exotic dumbbell-discocyte transition (e) was found which proceeded via local instabilities. Pears, discocytes, and stomatocytes are stable with respect to small temperature variations unless the excess area is close to values corresponding to limiting shapes of budded vesicles where temperature variations of less than or equal to 0.1 degree C lead to spontaneous budding to the inside or the outside. For {POPC} we observed only budding transitions to the inside leading either to chains of vesicles or to distributions of equally sized daughter vesicles protruding to the inside of the vesicle. Preliminary experiments concerning the effect of solutes are also reported. The first three types of shape transitions can be explained in terms of the bilayer coupling model assuming small differences in thermal expansivities of the two monolayers. This does not hold for the observed instabilities close to the limiting shapes.

W. Helfrich (1978): Steric Interaction of Fluid Membranes in Multilayer Systems
Type: article by Zeitschrift Naturforschung Teil A.
link: http://adsabs.harvard.edu/abs/1978ZNatA..33..305H

U. Seifert (1997): Configurations of fluid membranes and vesicles
Type: article by Advances in Physics.
link: http://adsabs.harvard.edu/abs/1997AdPhy..46...13S
Abstract:

Vesicles consisting of a bilayer membrane of amphiphilic lipid molecules

are remarkably flexible surfaces that show an amazing variety of shapes of different symmetry and topology. Owing to the fluidity of the membrane, shape transitions such as budding can be induced by temperature changes or the action of optical tweezers. Thermally excited shape fluctuations are both strong and slow enough to be visible by video microscopy. Depending on the physical conditions, vesicles adhere to and unbind from each other or a {substrate.This} article describes the systematic physical theory developed to understand the static and dynamic aspects of membrane and vesicle configurations. The preferred shapes arise from a competition between curvature energy, which derives from the bending elasticity of the membrane, geometrical constraints such as fixed surface area and fixed enclosed volume, and a signature of the bilayer aspect. These shapes of lowest energy are arranged into phase diagrams, which separate regions of different symmetry by continuous or discontinuous transitions. The geometrical constraints affect the fluctuations around these shapes by creating an effective {tension.For} vesicles of non-spherical topology, the conformal invariance of the curvature energy leads to conformal diffusion, which signifies a one-fold degeneracy of the ground state. Unbinding and adhesion transitions arise from the balance between attractive interactions and entropic repulsion or a cost in bending energy, respectively. Both the dynamics of equilibrium fluctuations and the dynamics of shape transformations are governed not only by viscous damping in the surrounding liquid but also by internal friction if the two monolayers slip over each other. More complex membranes such as that of the red blood cell exhibit a variety of new phenomena because of coupling between internal degrees of freedom and external geometry.

E. Evans, W. Rawicz (1990): Entropy-driven tension and bending elasticity in condensed-fluid membranes
Type: article by Physical Review Letters.
doi: 10.1103/PhysRevLett.64.2094
link: http://link.aps.org/abstract/PRL/v64/p2094
Abstract:

Sensitive micropipet methods have been used to measure the relation between tension and the projected surface area in fluid membranes of vesicles over a 4-order-of-magnitude range in tension (10-3–10 dyn/cm). In the low-tension regime ({textless}0.5 dyn/cm), the data confirm the prediction of equilibrium theory that the projected area should increase logarithmically with tension as shape fluctuations become progressively restricted. The slope of log(tension) versus area dilation yields and the elastic bending modulus of the membrane. In the high-tension regime, the projected area crosses over to vary linearly with tension due to direct expansion of area per molecule.

R. Lipowsky Generic interactions of flexible membranes
Type: article

E. Sackmann Physical basis of self-organization and function of membranes: physics of vesicles
Type: article

W. Helfrich (1973): Elastic properties of lipid bilayers: theory and possible experiments
Type: article by Zeitschrift Für Naturforschung. Teil C: Biochemie, Biophysik, Biologie, Virologie.
link: http://www.ncbi.nlm.nih.gov/pubmed/4273690

H. Noguchi, G. Gompper (2005): Shape transitions of fluid vesicles and red blood cells in capillary flows
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
doi: 10.1073/pnas.0504243102
link: http://www.pnas.org/content/102/40/14159.abstract
Abstract:

The dynamics of fluid vesicles and red blood cells {(RBCs)} in cylindrical capillary flow is studied by using a three-dimensional mesoscopic simulation approach. As flow velocity increases, a model {RBC} is found to transit from a nonaxisymmetric discocyteto an axisymmetric parachute shape (coaxial with the flow axis), while a fluid vesicle is found to transit from a discocyte to a prolate ellipsoid. Both shape transitions reduce the flow resistance. The critical velocities of the shape transitions are linearly dependent on the bending rigidity and on the shear modulus of the membrane. Slipper-like shapes of the {RBC} model are observed around the transition velocities. Our results are in good agreement with experiments on {RBCs.}

C. Rotsch (2000): {Drug-Induced} Changes of Cytoskeletal Structure and Mechanics in Fibroblasts: An Atomic Force Microscopy Study
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(00)76614-8
link: http://www.cell.com/biophysj/abstract/S0006-3495(00)76614-8
Abstract:

The effect of various drugs affecting the integrity of different components of the cytoskeleton on the elasticity of two fibroblast cell lines was investigated by elasticity measurements with an atomic force microscope {(AFM).} Disaggregation of actin filaments always resulted in a distinct decrease in the cells average elastic modulus indicating the crucial importance of the actin network for the mechanical stability of living cells. Disruption or chemical stabilization of microtubules did not affect cell elasticity. For the f-actin-disrupting drugs different mechanisms of drug action were observed. Cytochalasins B and D and Latrunculin A disassembled stress fibers. For Cytochalasin D this was accompanied by an aggregation of actin within the cytosol. Jasplakinolide disaggregated actin filaments but did not disassemble stress fibers. Fibrous structures found in {AFM} images and elasticity maps of fibroblasts could be identified as stress fibers by correlation of {AFM} data and fluorescence images.

D. Boal (2001): Mechanics of the Cell
Type: book by Cambridge University Press.

D. W. Thompson (1992): On Growth and Form: The Complete Revised Edition
Type: book by Dover Publications.

B. Fourcade, M. Mutz, D. Bensimon (1992): Experimental and theoretical study of toroidal vesicles
Type: article by Physical Review Letters.
doi: 10.1103/PhysRevLett.68.2551
link: http://link.aps.org/abstract/PRL/v68/p2551
Abstract:

We report the observation of toroidal and higher genus vesicles of diacetylenic phospholipids, a class of polymerizable amphiphiles. When unpolymerized, the vesicles exhibit different toroidal shapes in quantitative agreement with recent theoretical predictions. When partially polymerized, only a specific family of shapes has been observed: the Clifford torus or the branch of nonaxisymmetric shapes obtained by its conformal transformations. Assuming that partially polymerized vesicles are permeable on short time scale, we give a physical explanation of our findings. We also report the results of a variational calculation which approximates the nonaxisymmetric shape problem for finite spontaneous curvature.

J. O. Rädler, T. J. Feder, H. H. Strey, E. Sackmann (1995): Fluctuation analysis of tension-controlled undulation forces between giant vesicles and solid substrates
Type: article by Physical Review E.
doi: 10.1103/PhysRevE.51.4526
link: http://link.aps.org/abstract/PRE/v51/p4526
Abstract:

Using reflection interference contrast microscopy, we studied the thermal fluctuations of giant vesicles that weakly adhere to flat solid substrates. The absolute membrane-substrate separation distance was imaged and the average contact contour, including the contact area, the contact rounding, and the asymptotic contact angle, was determined. The static fluctuations in the flat, adhering part of the vesicle were analyzed. The spectrum of mean square amplitudes yielded the lateral membrane tension and the second derivative of the interaction potential. The vertical roughness and lateral correlation length were measured from the spatial autocorrelation of the undulations. The roughness was shown to obey the behavior predicted by functional renormalization in the observed tension regime of 10-6 to 10-4 J/m2. Moreover, the measured separation distances can be explained within the framework of undulation and van der Waals forces and confirmed the model of tension-induced adhesion. However, the adhesion energies as well as the measured separation distances exhibit a weaker dependence on the membrane tension than predicted.

F. Brochard, J. F. Lennon (1975): Frequency spectrum of the flicker phenomenon in erythrocytes
Type: article by Journal de Physique.

Z. Guttenberg, B. Lorz, E. Sackmann, A. Boulbitch (2001): First-order transition between adhesion states in a system mimicking cell-tissue interaction
Type: article by Europhysics Letters.
link: http://adsabs.harvard.edu/abs/2001EL.....54..826G
Abstract:

We establish a model of cell-tissue interaction consisting of vesicles

carrying lipopolymers (to mimic the glycocalix) and mobile specific ligands of the blood platelet integrin {alphaIIbbeta3} covering the substrate. We find the phase diagram with a first-order transition between a gravity-controlled weak state of the vesicle-substrate adhesion and a strong-adhesion state governed by receptor-ligand interaction. Adhesion energy ɛadh is measured as a function of ligand and repeller concentration by interferometric contour analysis on the basis of a new refined model of soft shell adhesion (accounting for the membrane bending and stretching at the adhesion rim of the ellipsoidal vesicle). At ligand densities comparable to integrin density, ɛadh decreases sharply. Increasing the repeller content weakens the adhesion strength.

W. Häckl, U. Seifert, E. Sackmann (1997): Effects of Fully and Partially Solubilized Amphiphiles on Bilayer Bending Stiffness and Temperature Dependence of the Effective Tension of Giant Vesicles
Type: article by Journal de Physique {II}.
link: http://adsabs.harvard.edu/abs/1997JPhy2...7.1141H
Abstract:

We report the modification of the bending elastic modulus k_c of lipid

bilayers (here {DMPC)} by small amounts (c leq 5 mol %) of (i) small amphiphiles which exchange between the bilayer and the aqueous phase (e.g. the ion carrier valinomycin and the Ca{textasciicircum}{++} carrier A23187) and (ii) amphiphiles solubilized in the membrane (cholanic acid). Large reductions of the bending stiffness may be induced by a few percent of the solutes, e.g. 1 mol % of valinomycin reduce k_c by a factor of two. The effect is rationalised in terms of local thinning of the bilayer. The strong effect of solutes on k_c contrasts with its weak dependence on the lipid structure since the {C18:0/C18:1-lipid} stearoyl-oleoyl-phosphatidyl-choline {(SOPC)} exhibits only a 15% higher value of k_c than {DMPC.} The effect of temperature on the flicker behaviour was analysed in order to establish correlations between the effective tension and the excess area of the quasi-spherical vesicles. The temperature dependence of the bilayer excess area for a {DMPC} vesicle leads to the thermal expansion coefficient, beta, for which a value of beta = 10.4 � 10{textasciicircum}{-3} K{textasciicircum}{-1} is obtained. A much stronger tendency for budding on mum-scale (micro budding) during thermal area expansion of {POPC} and {SOPC} compared to {DMPC} was observed.

R. Lipowsky (1995): The morphology of lipid membranes
Type: article by Current Opinion in Structural Biology.

U. Seifert, R. Lipowsky (1995): Morphology of vesicles
Type: article by Handbook of biological physics.

H. S. Seung, D. R. Nelson (1988): Defects in flexible membranes with crystalline order
Type: article by Physical Review. A.
link: http://www.ncbi.nlm.nih.gov/pubmed/9900464

H. Engelhardt, E. Sackmann (1988): On the measurement of shear elastic moduli and viscosities of erythrocyte plasma membranes by transient deformation in high frequency electric fields
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(88)82982-5
link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B94RW-4V8S1WH-F&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1141919462&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=9558b214d98f58e6d76227cf54fd4d27
Abstract:

Sensitive micropipet methods have been used to measure the relation between tension and the projected surface area in fluid membranes of vesicles over a 4-order-of-magnitude range in tension (10-3–10 dyn/cm). In the low-tension regime ({textless}0.5 dyn/cm), the data confirm the prediction of equilibrium theory that the projected area should increase logarithmically with tension as shape fluctuations become progressively restricted. The slope of log(tension) versus area dilation yields and the elastic bending modulus of the membrane. In the high-tension regime, the projected area crosses over to vary linearly with tension due to direct expansion of area per molecule.

J. L. van Hemmen, C. Leibold (2007): Elementary excitations of biomembranes: Differential geometry of undulations in elastic surfaces
Type: article by Physics Reports.
doi: 10.1016/j.physrep.2006.12.007
link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TVP-4NB2WHC-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1141919626&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5d36854e3fb202a8bb5d25531acbafd5

R. R. Netz (1995): Complete unbinding of fluid membranes in the presence of short-ranged forces
Type: article by Physical Review E.
doi: 10.1103/PhysRevE.51.2286
link: http://link.aps.org/abstract/PRE/v51/p2286
Abstract:

Lipid or surfactant bilayers which are bound by an external pressure and intereact via an additional short-ranged potential are studied theoretically. If the latter potential is not strong enough to bind the lamellae by itself, it has asymptotically no effect on the (complete) unbinding transition, which occurs in the limit of vanishing pressure; the separation and correlation lengths diverge as power laws as a function of the pressure, with the amplitudes being determined by characteristic amplitude ratios. If the potential strength exceeds the critical value, the bilayers are bound even for zero external pressure (incomplete unbinding). Exactly at the critical potential strength, all length scales again diverge as a function of the pressure. The critical exponents are found to be identical to those for a less attractive potential, but the asymptotic amplitude ratios have different values; also, the fluctuation amplitude, which measures the strength of the fluctuation-induced repulsion between the bilayers, is reduced by a factor of 12 as compared to the subcritical case. These results are obtained directly by Monte Carlo simulations of two fluid membranes and agree with exact calculations for the analogous system of two strings in 1+1 dimensions. Experimentally, the effects of short-ranged van der Waals attraction on the fluctuation amplitude cfl should be observable for suitable systems by small-angle x-ray scattering on lamellar phases.

B. T. Stokke, A. Mikkelsen, A. Elgsaeter (1986): Spectrin, human erythrocyte shapes, and mechanochemical properties
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(86)83644-X
link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B94RW-4V8S1WW-2R&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1141919907&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=1fbbb560010fe13287501c1c2fa9c78d

A. Zidovska, E. Sackmann (2006): Brownian Motion of Nucleated Cell Envelopes Impedes Adhesion
Type: article by Physical Review Letters.
doi: 10.1103/PhysRevLett.96.048103
link: http://link.aps.org/abstract/PRL/v96/e048103

Kapitel 12

T. Baumgart, S. T. Hess, W. W. Webb (2003): Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension
Type: article by Nature.
doi: 10.1038/nature02013
link: http://dx.doi.org/10.1038/nature02013
Abstract:

Lipid bilayer membranes—ubiquitous in biological systems and closely associated with cell function—exhibit rich shape-transition behaviour, including bud formation1 and vesicle fission2. Membranes formed from multiple lipid components can laterally separate into coexisting liquid phases, or domains, with distinct compositions. This process, which may resemble raft formation in cell membranes, has been directly observed in giant unilamellar vesicles3, 4. Detailed theoretical frameworks5, 6, 7, 8, 9, 10, 11 link the elasticity of domains and their boundary properties to the shape adopted by membranes and the formation of particular domain patterns, but it has been difficult to experimentally probe and validate these theories. Here we show that high-resolution fluorescence imaging using two dyes preferentially labelling different fluid phases directly provides a correlation between domain composition and local membrane curvature. Using freely suspended membranes of giant unilamellar vesicles, we are able to optically resolve curvature and line tension interactions of circular, stripe and ring domains. We observe long-range domain ordering in the form of locally parallel stripes and hexagonal arrays of circular domains, curvature-dependent domain sorting, and membrane fission into separate vesicles at domain boundaries. By analysing our observations using available membrane theory, we are able to provide experimental estimates of boundary tension between fluid bilayer domains.

E. Karatekin, O. Sandre, H. Guitouni, N. Borghi, P.-H. Puech, F. Brochard-Wyart (2003): Cascades of Transient Pores in Giant Vesicles: Line Tension and Transport
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302742
Abstract:

Under ordinary circumstances, the membrane tension of a giant unilamellar vesicle is essentially nil. Using visible light, we stretch the vesicles, increasing the membrane tension until the membrane responds by the sudden opening of a large pore (several micrometers in size). Only a single pore is observed at a time in a given vesicle. However, a cascade of transient pores appear, up to 30–40 in succession, in the same vesicle. These pores are transient: they reseal within a few seconds as the inner liquid leaks out. The membrane tension, which is the driving force for pore opening, is relaxed with the opening of a pore and the leakage of the inner liquid; the line tension of the pore's edge is then able to drive the closure of a pore. We use fluorescent membrane probes and real-time videomicroscopy to study the dynamics of the pores. These can be visualized only if the vesicles are prepared in a viscous solution to slow down the leakout of the internal liquid. From measurements of the closure velocity of the pores, we are able to infer the line tension, T. We have studied the effect of the shape of inclusion molecules on T. Cholesterol, which can be modeled as an inverted cone-shaped molecule, increases the line tension when incorporated into the bilayers. Conversely, addition of cone-shaped detergents reduces T. The effect of some detergents can be dramatic, reducing Tby two orders of magnitude, and increasing pore lifetimes up to several minutes. We give some examples of transport through transient pores and present a rough measurement of the leakout velocity of the inner liquid through a pore. We discuss how our results can be extended to less viscous aqueous solutions which are more relevant for biological systems and biotechnological applications.

L. Chernomordik, A. Chanturiya, J. Green, J. Zimmerberg (1995): The hemifusion intermediate and its conversion to complete fusion: regulation by membrane composition
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(95)79966-0
link: http://www.ncbi.nlm.nih.gov/pubmed/8519992
Abstract:

To fuse, membranes must bend. The energy of each lipid monolayer with respect to bending is minimized at the spontaneous curvature of the monolayer. Two lipids known to promote opposite spontaneous curvatures, lysophosphatidylcholine and arachidonic acid, were added to different sides of planar phospholipid membranes. Lysophosphatidylcholine added to the contacting monolayers of fusing membranes inhibited the hemifusion we observed between lipid vesicles and planar membranes. In contrast, fusion pore formation depended upon the distal monolayer of the planar membrane; lysophosphatidylcholine promoted and arachidonic acid inhibited. Thus, the intermediates of hemifusion and fusion pores in phospholipid membranes involve different membrane monolayers and may have opposite net curvatures, Biological fusion may proceed through similar intermediates.

S. Mabrey, P. L. Mateo, J. M. Sturtevant (1978): High-sensitivity scanning calorimetric study of mixtures of cholesterol with dimyristoyl- and dipalmitoylphosphatidylcholines
Type: article by Biochemistry.
doi: 10.1021/bi00605a034
link: http://dx.doi.org/10.1021/bi00605a034

R. B. Sutton, D. Fasshauer, R. Jahn, A. T. Brunger (1998): Crystal structure of a {SNARE} complex involved in synaptic exocytosis at 2.4 A resolution
Type: article by Nature.
doi: 10.1038/26412
link: http://www.ncbi.nlm.nih.gov/pubmed/9759724
Abstract:

The evolutionarily conserved {SNARE} proteins and their complexes are involved in the fusion of vesicles with their target membranes; however, the overall organization and structural details of these complexes are unknown. Here we report the X-ray crystal structure at 2.4 A resolution of a core synaptic fusion complex containing syntaxin-1 A, {synaptobrevin-II} and {SNAP-25B.} The structure reveals a highly twisted and parallel four-helix bundle that differs from the bundles described for the haemagglutinin and {HIV/SIV} gp41 membrane-fusion proteins. Conserved leucine-zipper-like layers are found at the centre of the synaptic fusion complex. Embedded within these leucine-zipper layers is an ionic layer consisting of an arginine and three glutamine residues contributed from each of the four alpha-helices. These residues are highly conserved across the entire {SNARE} family. The regions flanking the leucine-zipper-like layers contain a hydrophobic core similar to that of more general four-helix-bundle proteins. The surface of the synaptic fusion complex is highly grooved and possesses distinct hydrophilic, hydrophobic and charged regions. These characteristics may be important for membrane fusion and for the binding of regulatory factors affecting neurotransmission.

R. Cahn, W. Ludwig (1985): Theorie der Wärme.
Type: book by Springer, Berlin.

H. G. Döbereiner, J. Käs, D. Noppl, I. Sprenger, E. Sackmann (1993): Budding and fission of vesicles
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(93)81203-7
link: http://www.ncbi.nlm.nih.gov/pubmed/8274633
Abstract:

We report on budding and fission of protein-free vesicles swollen from a natural lipid mixture of bovine brain sphingomyelins. Budding was induced by increasing the area-to-volume ratio through heating. Morphological changes were monitored by phase contrast microscopy and correlated with the thermal behavior of the bilayer by differential scanning calorimetry. Freeze fracture electron microscopy revealed that budding and fission are not restricted to giant vesicles but also occur on length scales relevant for cellular processes. We also observed osmotically induced budding and fission in mixtures of dimyristoyl phosphatidylcholine with cholesterol. We find that these shape transitions are driven by liquid/gel domain formation and/or coupling of the spontaneous curvature of the membrane to the local lipid composition. Our results provide evidence that coat proteins are not necessary for budding and fission of vesicles. The physics of the lipid bilayer is rich enough to explain the observed behavior.

S. May, A. Ben-Shaul (2000): A molecular model for lipid-mediated interaction between proteins in membranes
Type: article by Physical Chemistry Chemical Physics.
link: http://dx.doi.org/10.1039/b003570j
Abstract:

The loss of conformational freedom experienced by lipid chains in the vicinity of one, or two, impenetrable walls, representing the surfaces of hydrophobic transmembrane proteins, is calculated using a mean-field molecular-level chain packing theory. The hydrophobic thickness of the protein is set equal to that of the unperturbed lipid membrane (i.e., no " hydrophobic mismatch"). The probability distributions of chain conformations, at all distances from the walls, are calculated by generating all conformations according to the rotational-isomeric-state model, and subjecting the system free energy to the requirement that the hydrophobic core of the membrane is liquid-like, and hence uniformly packed by chain segments. As long as the two protein surfaces are far apart, their interaction zones do not overlap, each extending over several molecular diameters. When the interaction zones begin to overlap, inter-protein repulsion sets in. At some intermediate distance the interaction turns strongly attractive, resulting from the depletion of (highly constrained) lipid tails from the volume separating the two surfaces. The chains confined between the hydrophobic surfaces are tilted away from the walls. Their tilt angle decreases monotonically with the distance from the walls, and with the distance between the walls. A nonmonotonic variation of the lipid-mediated interaction free energy between hydrophobic surfaces in membranes is also obtained using a simple, analytical, model in which chain conformations are grouped according to their director (end-to-end vector) orientations.

B. Bechinger (1996): Towards membrane protein design: {pH-sensitive} topology of histidine-containing polypeptides
Type: article by Journal of Molecular Biology.
doi: 10.1006/jmbi.1996.0614
link: http://www.ncbi.nlm.nih.gov/pubmed/8947574
Abstract:

Hydrophobic and amphipathic alpha-helices act as independent functional units in immunogenic or fusogenic polypeptides and constitute important structural building blocks in larger membrane proteins. In order to quantitatively assess the interactions that determine the alignment of membrane-associated alpha-helices, hydrophobic model peptides containing histidine residues at selected sites were prepared by solid-phase peptide synthesis. {CD} and solution {NMR} spectroscopy show that these peptides assume alpha-helical secondary structures in micellar environments. The chemical shift alterations of the histidine side-chain protons during {pH} titration experiments indicate that the {pK} values of the histidine imidazole protons range from 4.9 to 6.6 in the presence of dodecylphosphocholine micelles. {15N} solid-state {NMR} spectroscopy was used to determine the membrane alignment of these peptide alpha-helices in uniaxially oriented phospholipid bilayers. The observed {pH-dependent} change of orientation of one of these model peptides is quantitatively described by a dynamic equilibrium governed by both electrostatic and hydrophobic protein-lipid interactions. The thermodynamic equations presented provide a means for the prediction of membrane protein structure and topology, as well as the future design of peptide channels and pharmaceuticals.

M. Ø. Jensen, O. G. Mouritsen (2004): Lipids do influence protein function-the hydrophobic matching hypothesis revisited
Type: article by Biochimica Et Biophysica Acta.
doi: 10.1016/j.bbamem.2004.06.009
link: http://www.ncbi.nlm.nih.gov/pubmed/15519316
Abstract:

A topical review of the current state of lipid-protein interactions is given with focus on the physical interactions between lipids and integral proteins in lipid-bilayer membranes. The concepts of hydrophobic matching and curvature stress are revisited in light of recent data obtained from experimental and theoretical studies which demonstrate that not only do integral proteins perturb the lipids, but the physical state of the lipids does also actively influence protein function. The case of the trans-membrane water-channel protein aquaporin {GlpF} from E. coli imbedded in lipid-bilayer membranes is discussed in some detail. Numerical data obtained from Molecular Dynamics simulations show on the one side that the lipid bilayer adapts to the channel by a hydrophobic matching condition which reflects the propensity of the lipid molecules for forming curved structures. On the other side, it is demonstrated that the transport function of the channel is modulated by the matching condition and/or the curvature stress in a lipid-specific manner.

T. Sintes, A. Baumgärtner (1997): Protein attraction in membranes induced by lipid fluctuations
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(97)78257-2
link: http://www.ncbi.nlm.nih.gov/pubmed/9370422
Abstract:

The nonspecific lipid-mediated attraction between two proteins embedded in a bilayer membrane have been investigated for a model system using Monte Carlo simulations. We found two types of attraction with different regimes. A depletion-induced attraction in the range r {textless} {sigmaL,} where {sigmaL} is the diameter of a lipid and r is the distance between the surfaces of the two proteins, and a fluctuation-induced attraction in the range 1 {textless} {r/sigmaL} {textless} 6, which originates from the gradients of density and orientational fluctuations of the lipids around each protein. The effective potential of the latter type of attraction decays exponentially with U(r) approximately exp(r/vi) where the correlation length is {vi/sigmaL} approximately 3.2 in the present model system.

E. Sackmann (2006): Thermo-elasticity and adhesion as regulators of cell membrane architecture and function
Type: article by Journal of Physics: Condensed Matter.
link: http://www.iop.org/EJ/abstract/0953-8984/18/45/R02/
Abstract:

Elastic forces and structural phase transitions control the

architecture and function of bio-membranes from the molecular to the microscopic scale of organization. The multi-component lipid bilayer matrix behaves as a pseudo-ternary system. Together with elastically and electrostatically mediated specific lipid-protein interaction mechanisms, fluid-fluid phase separation can occur at physiological temperatures. This can drive the transient generation of micro-domains of distinct composition within multi-component lipid-protein alloys, enabling cells to optimize the efficiency of biochemical reactions by facilitating or inhibiting the access of enzymes by distinct substrates or regulatory proteins. Together with global shape changes governed by the principle of minimum bending energy and induced curvature by macromolecular adsorption, phase separation processes can also play a key role for the sorting of lipids and proteins between intracellular compartments during the vesicle mediated intracellular material transport. Cell adhesion is another example of mechanical force controlled membrane processes. By interplay of attractive lock and key forces, long range disjoining pressures mediated by repeller molecules or membrane undulations and elastic interfacial forces, adhesion induced domain formation can play a dual role for the immunological stimulation of lymphocytes and for the rapid control of the adhesion strength. The present picture of the thermo-elastic control of membrane processes based on concepts of local thermal equilibrium is still rudimentary and has to be extended in the future to account for the intrinsic non-equilibrium situation associated with the constant restructuring of the cellular compartments on a timescale of minutes.

A. Ben-Shaul Molecular theory of chain packing, elasticity and lipid-protein interaction in lipid bilayers
Type: article

H. Reinl, T. Brumm, T. Bayerl (1992): Changes of the physical properties of the liquid-ordered phase with temperature in binary mixtures of {DPPC} with {cholesterolA} {2H-NMR,} {FT-IR,} {DSC,} and neutron scattering study
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(92)81910-0
link: http://www.cell.com/biophysj/abstract/S0006-3495(92)81910-0
Abstract:

The structure of the so-called liquid-ordered (lo) phase of binary mixtures of {DPPC-d62} with cholesterol was studied between 2050 mol% cholesterol using {2H-NMR,} {FT-IR,} {DSC,} and neutron specular reflection. Different model systems such as multilamellar vesicles, spherical supported vesicles, and oriented multilayers were used. We observed significant changes of the lo phase structure in the physiological relevant temperature region between {3045C.} {2H-NMR} in combination with lineshape simulations provides evidence for a drastic effect of cholesterol on the shape of multilamellar vesicles due to magnetic field orientation. Moreover, the data indicates a significant change of the extent of this partial orientation for {DPPC-d62} multilamellar vesicles containing 25 mol% cholesterol between {3642C.} The semiaxes ratio of the (due to magnetic field orientation) ellipsoidal multilamellar vesicles changes over this temperature range by ≈25%. {2H-NMR} and {FT-IR} measurements indicate changes of the average orientational order at the bilayer center in the same temperature range and a significant increase of the number of end-gauche conformers while the majority of the methylene groups remain in an all-trans conformation. Additionally, specular reflection of neutrons shows a concomitant reduction of the bilayer thickness by 4Å. Based on a model of the arrangement of {DPPC} and cholesterol in the lo phase, a molecular mechanism is proposed in which increasing the temperature between 30 and {45C} has the effect of driving cholesterol from the bilayer center towards the head group region

R. Lipowsky Generic interactions of flexible membranes
Type: article

R. F. M. de Almeida, A. Fedorov, M. Prieto (2003): Sphingomyelin/phosphatidylcholine/cholesterol phase diagram: boundaries and composition of lipid rafts
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(03)74664-5
link: http://www.ncbi.nlm.nih.gov/pubmed/14507704
Abstract:

The ternary system palmitoylsphingomyelin {(PSM)/palmitoyloleoylphosphatidylcholine} {(POPC)/cholesterol} is used to model lipid rafts. The phase behavior of the three binary systems {PSM/POPC,} {PSM/cholesterol,} and {POPC/cholesterol} is first experimentally determined. Phase coexistence boundaries are then determined for ternary mixtures at room temperature (23 degrees C) and the ternary phase diagram at that temperature is obtained. From the diagram at 23 degrees C and the binary phase diagrams, a reasonable expectation is drawn for the ternary phase diagram at 37 degrees C. Several photophysical methodologies are employed that do not involve detergent extraction, in addition to literature data (e.g., differential scanning calorimetry) and thermodynamic rules. For the ternary phase diagrams, some tie-lines are calculated, including the one that contains the {PSM/POPC/} cholesterol 1:1:1 mixture, which is often used in model raft studies. The diagrams here described are used to rationalize literature results, some of them apparently discrepant, and to discuss lipid rafts within the framework of liquid-ordered/liquid-disordered phase coexistence.

R. Waugh (1979): Thermoelasticity of red blood cell membrane
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(79)85239-X
link: http://www.cell.com/biophysj/abstract/S0006-3495(79)85239-X
Abstract:

The elastic properties of the human red blood cell membrane have been measured as functions of temperature. The area compressibility modulus and the elastic shear modulus, which together characterize the surface elastic behavior of the membrane, have been measured over the temperature range of 250 degrees C with micropipette aspiration of flaccid and osmotically swollen red cells. In addition, the fractional increase in membrane surface area from 250 degrees C has been measured to give a value for the thermal area expansivity. The value of the elastic shear modulus at 25 degrees C was measured to be 6.6 X 10(-3) dyne/cm. The change in the elastic shear modulus with temperature was -6 X 10(-5) dyne/cm degrees C. Fractional forces were shown to be only on the order of 1015%. The area compressibility modulus at 25 degrees C was measured to be 450 dyne/cm. The change in the area compressibility modulus with temperature was -6 dyne/cm degrees C. The thermal area expansivity for red cell membrane was measured to be 1.2 X 10(-3)/degrees C. With this data and thermoelastic relations the heat of expansion is determined to be 110200 ergs/cm2; the heat of extension is 2 X 10(-2) ergs/cm2 for unit extension of the red cell membrane. The heat of expansion is of the order anticipated for a lipid bilayer idealized as twice the behavior of a monolayer at an oil-water interface. The observation that the heat of extension is positive demonstrates that the entropy of the material increases with extension, and that the dominant mechanism of elastic energy storage is energetic. Assuming that the red cell membrane shear rigidity is associated with "spectrin," unit extension of the membrane increases the configurational entropy of spectrin by 500 cal/mol.

W. Helfrich (1973): Elastic properties of lipid bilayers: theory and possible experiments
Type: article by Zeitschrift Für Naturforschung. Teil C: Biochemie, Biophysik, Biologie, Virologie.
link: http://www.ncbi.nlm.nih.gov/pubmed/4273690

S. A. Safran, T. L. Kuhl, J. N. Israelachvili (2001): Polymer-induced membrane contraction, phase separation, and fusion via Marangoni flow
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(01)75730-X
link: http://www.ncbi.nlm.nih.gov/pubmed/11463614
Abstract:

Experiments have shown that the depletion of polymer in the region between two apposed (contacting or nearly contacting) bilayer membranes leads to fusion. In this paper we show theoretically that the addition of nonadsorbing polymer in solution can promote lateral contraction and phase separation of the lipids in the outer monolayers of the membranes exposed to the polymer solution, i.e., outside the contact zone. This initial phase coexistence of higher- and lower-density lipid domains in the outer monolayer results in surface tension gradients in the outer monolayer. Initially, the inner layer lipids are not exposed to the polymer solution and remain in their original "unstressed" state. The differential stresses on the bilayers give rise to a Marangoni flow of lipid from the outer monolayers in the "contact zone" (where there is little polymer and hence a uniform phase) to the outer monolayers in the "reservoir" (where initially the surface tension gradients are large due to the polymer-induced phase separation). As a result, the low-density domains of the outer monolayers in the contact zone expose their hydrophobic chains, and those of the inner monolayers, to the solvent and to each other across the narrow water gap, allowing fusion to occur via a hydrophobic interaction. More generally, this type of mechanism suggests that fusion and other intermembrane interactions may be triggered by Marangoni flows induced by surface tension gradients that provide "action at a distance" far from the fusion or interaction zone.

M. R. Vist, J. H. Davis (1990): Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine mixtures: deuterium nuclear magnetic resonance and differential scanning calorimetry
Type: article by Biochemistry.
doi: 10.1021/bi00454a021
link: http://dx.doi.org/10.1021/bi00454a021

D. Langosch, J. M. Crane, B. Brosig, A. Hellwig, L. K. Tamm, J. Reed (2001): Peptide mimics of {SNARE} transmembrane segments drive membrane fusion depending on their conformational plasticity
Type: article by Journal of Molecular Biology.
doi: 10.1006/jmbi.2001.4889
link: http://www.ncbi.nlm.nih.gov/pubmed/11518525
Abstract:

{SNARE} proteins are essential for different types of intracellular membrane fusion. Whereas interaction between their cytoplasmic domains is held responsible for establishing membrane proximity, the role of the transmembrane segments in the fusion process is currently not clear. Here, we used an in vitro approach based on lipid mixing and electron microscopy to examine a potential fusogenic activity of the transmembrane segments. We show that the presence of synthetic peptides representing the transmembrane segments of the presynaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptors {(SNAREs)} synaptobrevin {II} (also referred to as {VAMP} {II)} or syntaxin {1A,} but not of an unrelated control peptide, in liposomal membranes drives their fusion. Liposome aggregation by millimolar Ca(2+) concentrations strongly potentiated the effect of the peptides; this indicates that juxtaposition of the bilayers favours their fusion in the absence of the cytoplasmic {SNARE} domains. Peptide-driven fusion is reminiscent of natural membrane fusion, since it was suppressed by lysolipid and involved both bilayer leaflets. This suggests transient presence of a hemifusion intermediate followed by complete membrane merger. Structural studies of the peptides in lipid bilayers performed by Fourier transform infrared spectroscopy indicated mixtures of alpha-helical and beta-sheet conformations. In isotropic solution, circular dichroism spectroscopy showed the peptides to exist in a concentration-dependent equilibrium of alpha-helical and beta-sheet structures. Interestingly, the fusogenic activity decreased with increasing stability of the alpha-helical solution structure for a panel of variant peptides. Thus, structural plasticity of transmembrane segments may be important for {SNARE} protein function at a late step in membrane fusion.

M. R. Brzustowicz, V. Cherezov, M. Caffrey, W. Stillwell, S. R. Wassall (2002): Molecular organization of cholesterol in polyunsaturated membranes: microdomain formation
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(02)75394-0
link: http://www.ncbi.nlm.nih.gov/pubmed/11751316
Abstract:

The molecular organization of cholesterol in phospholipid bilayers composed of 1,2-diarachidonylphosphatidylcholine {(20:4-20:4PC),} 1-stearoyl-2-arachidonylphosphatidylcholine {(18:0-20:4PC),} and {20:4-20:4PC/18:0-20:4PC} (1/1 mol) was investigated by solid-state {(2)H} {NMR} and by low- and wide-angle x-ray diffraction {(XRD).} On the basis of distinct quadrupolar powder patterns arising from [3 {alpha-(2)H(1)]cholesterol} intercalated into the membrane and phase separated as solid, solubility {chi(NMR)(chol)} = 17 +/- 2 mol% and tilt angle alpha(0) = 25 +/- 1 degrees in {20:4-20:4PC} were determined. The corresponding values in {18:0-20:4PC} were chi {(NMR)(chol)} {textgreater} or = 50 mol% and alpha(0) = 16 +/- 1 degrees. Cholesterol solubility determined by {XRD} was {chi(NMR)(chol)} = 15 +/- 2 mol% and {chi(NMR)(chol)} = 49 +/- 1 mol% for {20:4-20:4PC} and {18:0-20:4PC,} respectively. {XRD} experiments show that the solid sterol is monohydrate crystals presumably residing outside the bilayer. The {(2)H} {NMR} spectrum for equimolar [3 {alpha-(2)H(1)]cholesterol} added to mixed {20:4-20:4PC/18:0-20:4PC} (1/1 mol) membranes is consistent with segregation of cholesterol into {20:4-20:4PC} and {18:0-20:4PC} microdomains of {textless}160 A in size that preserve the molecular organization of sterol in the individual phospholipid constituents. Our results demonstrate unambiguously that cholesterol has low affinity to polyunsaturated fatty acids and support hypotheses of lateral phase separation of membrane constituents into sterol-poor/polyunsaturated fatty acid-rich and sterol-rich/saturated fatty acid-rich microdomains.

C. Böttcher, K. Ludwig, A. Herrmann, M. van Heel, H. Stark (1999): Structure of influenza haemagglutinin at neutral and at fusogenic {pH} by electron cryo-microscopy
Type: article by {FEBS} Letters.
link: http://www.ncbi.nlm.nih.gov/pubmed/10606732
Abstract:

The three-dimensional structures of the complete haemagglutinin {(HA)} of influenza virus {A/Japan/305/57} {(H2N2)} in its native (neutral {pH)} and membrane fusion-competent (low {pH)} form by electron cryo-microscopy at a resolution of 10 A and 14 A, respectively, have been determined. In the fusion-competent form the subunits remain closely associated preserving typical overall features of the trimeric ectodomain at neutral {pH.} Rearrangements of the tertiary structure in the distal and the stem parts are associated with the formation of a central cavity through the entire ectodomain. We suggest that the cavity is essential for relocation of the so-called fusion sequence of {HA} towards the target membrane.

M. S. Bretscher, S. Munro (1993): Cholesterol and the Golgi apparatus
Type: article by Science {(New} York, {N.Y.)}.
link: http://www.ncbi.nlm.nih.gov/pubmed/8362242

D. N. Wang (1994): Band 3 protein: structure, flexibility and function
Type: article by {FEBS} Letters.
link: http://www.ncbi.nlm.nih.gov/pubmed/8206153
Abstract:

The electroneutral exchange of chloride and bicarbonate across the human erythrocyte membrane is facilitated by Band 3, a 911 amino acid glycoprotein. The 43 {kDa} amino-terminal cytosolic domain binds the cytoskeleton, haemoglobin and glycolytic enzymes. The 52 {kDa} carboxyl-terminal membrane domain mediates anion transport. The protein is a functional dimer, in which the two subunits probably interact with one another by an allosteric mechanism. It is proposed that the link between the mobile cytoplasmic and the membrane-spanning domains of the protein is flexible, based on recent biochemical, biophysical and structural data. This explains the long-standing puzzle that attachment to the cytoskeletal spectrin and actin does not appear to restrict the rotational movement of the Band 3 protein in the erythrocyte membrane. In the Band 3 isoform from the Southeast Asian Ovalocytes {(SAO)} this link is altered, resulting a tighter attachment of the cytoskeleton to the plasma membrane and a more rigid red blood cell.

A. Schlegel, M. P. Lisanti (2000): A molecular dissection of caveolin-1 membrane attachment and oligomerization. Two separate regions of the caveolin-1 C-terminal domain mediate membrane binding and oligomer/oligomer interactions in vivo
Type: article by The Journal of Biological Chemistry.
doi: 10.1074/jbc.M002558200
link: http://www.ncbi.nlm.nih.gov/pubmed/10801850
Abstract:

Caveolins form interlocking networks on the cytoplasmic face of caveolae. The cytoplasmically directed N and C termini of caveolins are separated by a central hydrophobic segment, which is believed to form a hairpin within the membrane. Here, we report that the caveolin scaffolding domain {(CSD,} residues 82-101), and the C terminus (residues 135-178) of caveolin-1 are each sufficient to anchor green fluorescent protein {(GFP)} to membranes in vivo. We also show that the first 16 residues of the C terminus (i.e. residues 135-150) are necessary and sufficient to attach {GFP} to membranes. When fused to the caveolin-1 C terminus, {GFP} co-localizes with two {trans-Golgi} markers and is excluded from caveolae. In contrast, the {CSD} targets {GFP} to caveolae, albeit less efficiently than full-length caveolin-1. Thus, caveolin-1 contains at least two membrane attachment signals: the {CSD,} dictating caveolar localization, and the C terminus, driving {trans-Golgi} localization. Additionally, we find that caveolin-1 oligomer/oligomer interactions require the distal third of the caveolin-1 C terminus. Thus, the caveolin-1 C-terminal domain has two separate functions: (i) membrane attachment (proximal third) and (ii) protein/protein interactions (distal third).

S. H. W. Wu, H. M. McConnell (1975): Phase separations in phospholipid membranes
Type: article by Biochemistry.
doi: 10.1021/bi00675a032
link: http://dx.doi.org/10.1021/bi00675a032

D. Boal (2001): Mechanics of the Cell
Type: book by Cambridge University Press.

C. Gliss, O. Randel, H. Casalta, E. Sackmann, R. Zorn, T. Bayerl (1999): Anisotropic motion of cholesterol in oriented {DPPC} bilayers studied by quasielastic neutron scattering: the liquid-ordered phase.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1300333&rendertype=abstract

K. Tu, M. L. Klein, D. J. Tobias (1998): Constant-pressure molecular dynamics investigation of cholesterol effects in a dipalmitoylphosphatidylcholine bilayer.
Type: article by Biophysical Journal.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1299887&rendertype=abstract

R. J. Mashl, R. F. Bruinsma (1998): Spontaneous-curvature theory of clathrin-coated membranes
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(98)77993-7
link: http://www.ncbi.nlm.nih.gov/pubmed/9635740
Abstract:

Clathrin-coated membranes are precursors to coated vesicles in the receptor-mediated endocytic pathway. In this paper we present a physical model for the first steps of the transformation of a clathrin-coated membrane into a coated vesicle. The theory is based on in vitro cytoplasmic acidification experiments of Heuser {(J.} Cell Biol. 108:401-411) that suggest the transformation proceeds by changes in the chemical environment of the clathrin lattice, wherein the chemical environment determines the amount of intrinsic, or spontaneous, curvature of the network. We show that a necessary step of the transformation, formation of free pentagons in the clathrin network, can proceed via dislocation unbinding, driven by changes in the spontaneous curvature. Dislocation unbinding is shown to favor formation of coated vesicles that are quite small compared to those predicted by the current continuum theories, which do not include the topology of the clathrin lattice.

T. P. McMullen, R. N. McElhaney (1995): New aspects of the interaction of cholesterol with dipalmitoylphosphatidylcholine bilayers as revealed by high-sensitivity differential scanning calorimetry
Type: article by Biochimica Et Biophysica Acta.
link: http://www.ncbi.nlm.nih.gov/pubmed/7880863
Abstract:

We have investigated the effects of cholesterol on the thermotropic phase behavior of annealed and unannealed aqueous dispersions of dipalmitoylphosphatidylcholine {(DPPC)} using high-sensitivity differential scanning calorimetry {(DSC),} concentrating particularly on the cholesterol concentration range from 0 to 20 mol%. We find that the incorporation of cholesterol into low-temperature annealed {DPPC} bilayers decreases the enthalpy of the subtransition without affecting the transition temperature, such that the subtransition is abolished by 20 mol% cholesterol. Similarly, the incorporation of cholesterol progressively decreases the temperature and enthalpy of the pretransition and abolishes it entirely at cholesterol concentrations above 5 mol%. The incorporation of increasing quantities of cholesterol also alters the main or chain-melting phase transition. At cholesterol concentrations of 2 to 20 mol% cholesterol, the {DSC} endotherm arising from the main transition consists of superimposed sharp and broad components, the former due to the melting of cholesterol-poor and the latter to the melting of the cholesterol-rich {DPPC} domains. The temperature and cooperativity of the sharp component decreases slightly with increasing cholesterol concentration whereas the enthalpy decreases markedly, becoming zero at 20-25 mol% cholesterol. In contrast, the temperature and enthalpy of the broad component increases, and the cooperativity decreases markedly over this same range of cholesterol concentrations. An apparent increase in cooperativity of the overall {DPPC} endotherm at 7 mol% cholesterol is shown to arise because of a convergence in the transition temperatures of the sharp and broad components of the {DSC} endotherms. Some of our experimental findings, particularly the absence of any evidence for the existence of a triple point near 7.5 mol% cholesterol, do not accord with a recently proposed {DPPC/cholesterol} phase diagram derived from {DSC} and {2H-NMR} data (see Vist, {M.R.} and Davis, {J.H.} (1990) Biochemistry 29, 451-464). In addition, we examined the effect of cholesterol on phosphatidylcholines {(PCs)} of different chain lengths and confirm that a eutectic point does not exist for any of these {PC/cholesterol} mixtures. We then propose a new, more complete {DPPC/cholesterol} phase diagram based on our high-sensitivity {DSC} data as well as some recent spectroscopic data on {PC/cholesterol} mixtures and explore some of its biological implications.

M. Bloom, E. Evans, O. G. Mouritsen (1991): Physical properties of the fluid lipid-bilayer component of cell membranes: a perspective
Type: article by Quarterly Reviews of Biophysics.
link: http://www.ncbi.nlm.nih.gov/pubmed/1749824

M. G. J. Ford, I. G. Mills, B. J. Peter, Y. Vallis, G. J. K. Praefcke, P. R. Evans, H. T. McMahon (2002): Curvature of clathrin-coated pits driven by epsin
Type: article by Nature.
doi: 10.1038/nature01020
link: http://www.ncbi.nlm.nih.gov/pubmed/12353027
Abstract:

Clathrin-mediated endocytosis involves cargo selection and membrane budding into vesicles with the aid of a protein coat. Formation of invaginated pits on the plasma membrane and subsequent budding of vesicles is an energetically demanding process that involves the cooperation of clathrin with many different proteins. Here we investigate the role of the brain-enriched protein epsin 1 in this process. Epsin is targeted to areas of endocytosis by binding the membrane lipid phosphatidylinositol-4,5-bisphosphate {(PtdIns(4,5)P(2)).} We show here that epsin 1 directly modifies membrane curvature on binding to {PtdIns(4,5)P(2)} in conjunction with clathrin polymerization. We have discovered that formation of an amphipathic alpha-helix in epsin is coupled to {PtdIns(4,5)P(2)} binding. Mutation of residues on the hydrophobic region of this helix abolishes the ability to curve membranes. We propose that this helix is inserted into one leaflet of the lipid bilayer, inducing curvature. On lipid monolayers epsin alone is sufficient to facilitate the formation of clathrin-coated invaginations.

W. Knoll, G. Schmidt, K. Ibel, E. Sackmann (1985): {SANS-study} of lateral phase separation in {DMPC-cholesterol} mixed membranes
Type: article by Biochemistry.

S. Hübner, A. D. Couvillon, J. A. Käs, V. A. Bankaitis, R. Vegners, C. L. Carpenter, P. A. Janmey (1998): Enhancement of phosphoinositide 3-kinase {(PI} 3-kinase) activity by membrane curvature and inositol-phospholipid-binding peptides
Type: article by European Journal of Biochemistry / {FEBS}.
link: http://www.ncbi.nlm.nih.gov/pubmed/9874255
Abstract:

The phosphorylation of phosphatidylinositol {(PtdIns)} on the 3' position of the inositol ring by phosphoinositide 3-kinase {(PI} 3-kinase) is shown to depend strongly on the curvature of liposomes containing a mixture of phosphatidylcholine {(PtdCho)} and {PtdIns.} Vesicles with an average diameter of 50 nm are phosphorylated 100 times faster than chemically identical vesicles with an average diameter greater than 300 nm. The low reactivity of large vesicles is not due to the difference in vesicle number for large and small vesicles at constant total lipid, nor to occlusion of lipid surfaces in multilammelar structures, and can be reversed by addition of low ({textless} 1:100) molar ratios of either the {PtdIns} transfer protein sec14p or a ten-residue peptide derived from the inositol-phospholipid-binding site of gelsolin. Similar measurements using {PI} 4-kinase showed a weak dependence on vesicle size. The strong dependence of {PI} 3-kinase function on membrane curvature suggests possible localization of {PI} 3-kinase activity at sites where clustering of receptors, for example, may locally deform the membrane, and suggests that once {PI} 3-kinase is localized and activated at surface sites, the reaction may become self-accelerating.

D. R. Gaskell (1996): In: Cahn {RW,} Hassen P, editors. Physical Metallurgy
Type: book by Elsevier Science {BV}.

H. S. Seung, D. R. Nelson (1988): Defects in flexible membranes with crystalline order
Type: article by Physical Review. A.
link: http://www.ncbi.nlm.nih.gov/pubmed/9900464

K. Jacobson, O. G Mouritsen, R. G. Anderson (2007): Lipid rafts: at a crossroad between cell biology and physics
Type: article by Nature cell biology.

S. Komura, H. Shirotori, P. D. Olmsted, D. Andelman (2004): Lateral phase separation in mixtures of lipids and cholesterol
Type: article by Europhysics Letters.
link: http://adsabs.harvard.edu/abs/2004EL.....67..321K
Abstract:

In an effort to understand "rafts" in biological membranes, we propose

phenomenological models for saturated and unsaturated lipid mixtures, and lipid-cholesterol mixtures. We consider simple couplings between the local composition and internal membrane structure, and their influence on transitions between liquid and gel membrane phases. Assuming that the gel transition temperature of the saturated lipid is shifted by the presence of the unsaturated lipid, and that cholesterol acts as an external field on the chain melting transition, a variety of phase diagrams are obtained. The phase diagrams for binary mixtures of saturated/unsaturated lipids and lipid/cholesterol are in semi-quantitative agreement with the experiments. Our results also apply to regions in the ternary phase diagram of lipid/lipid/cholesterol systems.

J. C. Owicki, H. M. McConnell (1979): Theory of protein-lipid and protein-protein interactions in bilayer membranes
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
doi: VL - 76
link: http://www.pnas.org/content/76/10/4750.abstract
Abstract:

A model for protein-lipid interactions in bilayer membranes where the proteins are very dilute is extended to higher protein concentration, where appreciable lipid-mediated protein-protein interactions occur. It is found that proteins may change the lipid phase transition temperature and that they weaken the phase transition. There exists a critical protein concentration above which the sharp lipid phase transition is abolished. The model also qualitatively reproduces several experimental observations on the physical behavior of bilayers formed from mixtures of cholesterol and phosphatidylcholines.

W. T. Góźdź, G. Gompper (1999): Shapes and shape transformations of two-component membranes of complex topology
Type: article by Physical Review E.
doi: 10.1103/PhysRevE.59.4305
link: http://link.aps.org/abstract/PRE/v59/p4305
Abstract:

The properties of two-component membranes, which form doubly periodic surfaces of complex topology, are studied in the strong-segregation limit. The membrane is described within the framework of curvature elasticity; the two components are distinguished by their spontaneous curvatures in this case. Four different domain morphologies are considered for a square lattice of passages: rings of component α inside the passage and caplets of component α outside the passage, as well as rings and caplets of component β. The dependences of the shape of the membrane and of the shape of the domain boundary are calculated as a function of composition. On the basis of a calculation of the curvature energy we conjecture the existence of doubly periodic, piecewise constant-mean-curvature surfaces. For small and intermediate line tensions, we predict several phase transitions between the investigated morphologies. We also discuss briefly the existence and shapes of vesicles of piecewise constant mean curvature.

G. G. Putzel, M. Schick (2008): Phenomenological Model and Phase Behavior of Saturated and Unsaturated Lipids and Cholesterol
Type: article by Biophysical Journal.
doi: 10.1529/biophysj.108.136317
link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B94RW-4VB4W2R-Y&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1141920767&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=2f9005f3b3630b9e25af97e0ef361b51

M. M. Perry, A. B. Gilbert (1979): Yolk transport in the ovarian follicle of the hen {(Gallus} domesticus): lipoprotein-like particles at the periphery of the oocyte in the rapid growth phase
Type: article by J Cell Sci.
link: http://jcs.biologists.org/cgi/content/abstract/39/1/257

J. Riegler, H. Möhwald (1986): Elastic Interactions of Photosynthetic Reaction Center Proteins Affecting Phase Transitions and Protein Distributions
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(86)83740-7
link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B94RW-4V8RX54-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1141921063&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=8557f623e3948d2ee4f1d43d7d7d7ee1

K. G. Rothberg, J. E. Heuser, W. C. Donzell, Y. S. Ying, J. R. Glenney, R. G. Anderson (1992): Caveolin, a protein component of caveolae membrane coats
Type: article by Cell.
link: http://www.ncbi.nlm.nih.gov/pubmed/1739974
Abstract:

Caveolae have been implicated in the transcytosis of macromolecules across endothelial cells and in the receptor-mediated uptake of 5-methyltetrahydrofolate. Structural studies indicate that caveolae are decorated on their cytoplasmic surface by a unique array of filaments or strands that form striated coatings. To understand how these nonclathrin-coated pits function, we performed structural analysis of the striated coat and searched for the molecular component(s) of the coat material. The coat cannot be removed by washing with high salt; however, exposure of membranes to cholesterol-binding drugs caused invaginated caveolae to flatten and the striated coat to disassemble. Antibodies directed against a 22 kd substrate for v-src tyrosine kinase in virus-transformed chick embryo fibroblasts decorated the filaments, suggesting that this molecule is a component of the coat. We have named the molecule caveolin. Caveolae represent a third type of coated membrane specialization that is involved in molecular transport.

E. A. Guggenheim (1985): Thermodynamics - An advanced treatment for chemists and physicists (7th edition)
Type: book by North Holland.
link: http://adsabs.harvard.edu/abs/1985anh..book.....G

Kapitel 13

M. Tanaka, E. Sackmann (2005): Polymer-supported membranes as models of the cell surface
Type: article by Nature.
doi: 10.1038/nature04164
link: http://dx.doi.org/10.1038/nature04164

G. I. Bell, M. Dembo, P. Bongrand (1984): Cell adhesion. Competition between nonspecific repulsion and specific bonding
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(84)84252-6
link: http://www.ncbi.nlm.nih.gov/pubmed/6743742
Abstract:

We develop a thermodynamic calculus for the modeling of cell adhesion. By means of this approach, we are able to compute the end results of competition between the formation of specific macromolecular bridges and nonspecific repulsion arising from electrostatic forces and osmotic (steric stabilization) forces. Using this calculus also allows us to derive in a straightforward manner the effects of cell deformability, the Young's modulus for stretching of bridges, diffusional mobility of receptors, heterogeneity of receptors, variation in receptor number, and the strength of receptor-receptor binding. The major insight that results from our analysis concerns the existence and characteristics of two phase transitions corresponding, respectively, to the onset of stable cell adhesion and to the onset of maximum cell-cell or cell-substrate contact. We are also able to make detailed predictions of the equilibrium contact area, equilibrium number of bridges, and the cell-cell or cell-substrate separation distance. We illustrate how our approach can be used to improve the analysis of experimental data, by means of two concrete examples.

A.-S. Smith, U. Seifert (2005): Force-induced de-adhesion of specifically bound vesicles: strong adhesion in competition with tether extraction
Type: article by Langmuir: The {ACS} Journal of Surfaces and Colloids.
doi: 10.1021/la051303f
link: http://www.ncbi.nlm.nih.gov/pubmed/16285811
Abstract:

A theoretical study of the thermodynamic equilibrium between force-induced tether formation and the adhesion of vesicles mediated by specific ligand-receptor interactions has been performed. The formation of bonds between mobile ligands in the vesicle and immobile receptors on the substrate is examined within a thermodynamic approximation. The shape of a vesicle pulled with a point force is calculated within a continuous approach. The two approaches are merged self-consistently by the use of the effective adhesion potential produced by the collective action of the bonds. As a result, the shapes of the vesicle and the tether, as well as the number of formed bonds in the contact zone, are determined as a function of the force, and approximate analytic expressions for them are provided. The de-adhesion process is characterized by the construction of a phase diagram that is a function of the density of the ligands in the vesicle, the surface coverage by receptors, the ligand-receptor binding affinity, and the reduced volume of the vesicle. In all cases, the phase diagram contains three regions separated by two nonintersecting lines of critical forces. The first is the line of onset forces associated with a second-order shape transition from a spherical cap to a tethered vesicle. The second line is attributed to the detachment forces at which a first-order unbinding transition from a tethered shape to a free vesicle occurs.

L. D. Landau, E. M. Lifschitz (1991): Lehrbuch der theoretischen Physik, 10 Bde., Bd.7, Elastizitätstheorie: {BD} 7
Type: book by Deutsch {(Harri)}.

P. G. de Gennes (1985): Wetting: statics and dynamics
Type: article by Reviews of Modern Physics.
link: http://adsabs.harvard.edu/abs/1985RvMP...57..827D
Abstract:

The wetting of solids by liquids is connected to physical chemistry

(wettability), to statistical physics (pinning of the contact line, wetting transitions, etc.), to long-range forces (van der Waals, double layers), and to fluid dynamics. The present review represents an attempt towards a unified picture with special emphasis on certain features of "dry spreading": (a) the final state of a spreading droplet need not be a monomolecular film; (b) the spreading drop is surrounded by a precursor film, where most of the available free energy is spent; and (c) polymer melts may slip on the solid and belong to a separate dynamical class, conceptually related to the spreading of superfluids.

A.-S. Smith, K. Sengupta, S. Goennenwein, U. Seifert, E. Sackmann (2008): Force-induced growth of adhesion domains is controlled by receptor mobility
Type: article by Proceedings of the National Academy of Sciences.
doi: 10.1073/pnas.0801706105
link: http://www.pnas.org/content/105/19/6906.abstract
Abstract:

In living cells, adhesion structures have the astonishing ability to grow and strengthen under force. Despite the rising evidence of the importance of this phenomenon, little is known about the underlying mechanism. Here, we show that force-induced adhesion-strengthening can occur purely because of the thermodynamic response to the elastic deformation of the membrane, even in the absence of the actively regulated cytoskeleton of the cell, which was hitherto deemed necessary. We impose {pN-forces} on two fluid membranes, locally pre-adhered by {RGD-integrin} binding. One of the binding partners is always mobile whereas the mobility of the other can be switched on or off. Immediate passive strengthening of adhesion structures occurs in both cases. When both binding partners are mobile, strengthening is aided by lateral movement of intact bonds as a transient response to force-induced membrane-deformation. By extending our microinterferometric technique to the suboptical regime, we show that the adhesion, as well as the resistance to force-induced de-adhesion, is greatly enhanced when both, rather than only one, of the binding partners are mobile. We formulate a theory that explains our observations by linking the macroscopic shape deformation with the microscopic formation of bonds, which further elucidates the importance of receptor mobility. We propose this fast passive response to be the first-recognition that triggers signaling events leading to mechanosensing in living cells.

T. A. Springer (1994): Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm
Type: article by Cell.
link: http://www.ncbi.nlm.nih.gov/pubmed/7507411

A. Albersdörfer, T. Feder, E. Sackmann (1997): Adhesion-induced domain formation by interplay of long-range repulsion and short-range attraction force: a model membrane study
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(97)78065-2
link: http://www.ncbi.nlm.nih.gov/pubmed/9199789
Abstract:

We study the role of the interplay of specific and universal forces for the adhesion of giant vesicles on solid supported membranes. To model the situation of cell adhesion, we incorporated lipopolymers (phospholipids with polyethyleneoxide headgroups) as artificial glycocalix, whereas attractive lock-and-key forces are mimicked by incorporating biotinylated lipids into both membranes and by mediating the strong coupling through streptavidin. Adhesion is studied by quantitative reflection interference contrast microscopy {(RICM),} which enables visualization of the contact zone and reconstruction of the height profile of the membrane beyond the contact line (outside the contact zone) up to a height of 1 micron. We demonstrate that adhesion is accompanied by lateral phase separation, leading to the formation of domains of tight adhesion (adhesion plaques) separated by areas of weak adhesion exhibiting pronounced flickering. By analyzing the height profile S(x) near the contact line in terms of the tension equilibrium {(Young} equation) and the moment equilibrium, respectively, the adhesion energy and membrane tension can be approximately measured locally. We show that the adhesion energy is about three orders of magnitude larger for the adhesion plaques than for the weekly adhering regions. The adhesion is studied as a function of the excess area of the vesicle generated by temperature variation. A very remarkable finding is that increased excess area is not always stored in the contact area, but leads to the formation of microbuds (diameter approximately 2 microns).

R. Bruinsma, A. Behrisch, E. Sackmann (2000): Adhesive switching of membranes: Experiment and theory
Type: article by Physical Review E.
doi: 10.1103/PhysRevE.61.4253
link: http://link.aps.org/abstract/PRE/v61/p4253
Abstract:

We report on a study of a model bioadhesion system: giant vesicles in contact with a supported lipid bilayer. Embedded in both membranes are very low concentrations of homophilic recognition molecules (contact site A receptors) competing with higher concentrations of repeller molecules: polyethylene glycol {(PEG)} lipids. These repellers mimic the inhibiting effect of the cell glycocalyx on adhesion. The effective adhesive interaction between the two membranes is probed by interferometric analysis of thermal fluctuations. We find two competing states of adhesion: initial weak adhesion is followed by slower aggregation of the adhesion molecules into small, tightly bound clusters that coexist with the regions of weak adhesion. We interpret our results in terms of a double-well intermembrane potential, and we present a theoretical analysis of the intermembrane interaction in the presence of mobile repeller molecules at a fixed chemical potential that shows that the interaction potential indeed should have just such a double-well shape. At a fixed repeller concentration we recover a conventional purely repulsive potential. We discuss the implications of our findings in terms of a general amplification mechanism of the action of sparse adhesion molecules by a nonspecific double-well potential. We also discuss the important role of the Helfrich undulation force for the proposed scenario.

P. L. Townes, J. Holtfreter (1955): Directed movements and selective adhesion of embryonic amphibian cells./. exp
Type: article

H. Lodish, A. Berk, C. A. Kaiser, M. Krieger, M. P. Scott, A. Bretscher (2007): Molecular Cell Biology
Type: book by Palgrave Macmillan.

S. F. Gilbert, S. R. Singer (2006): Developmental Biology
Type: book by Palgrave Macmillan.

C. R. Monks, B. A. Freiberg, H. Kupfer, N. Sciaky, A. Kupfer (1998): Three-dimensional segregation of supramolecular activation clusters in T cells
Type: article by Nature.
doi: 10.1038/25764
link: http://www.ncbi.nlm.nih.gov/pubmed/9738502
Abstract:

Activation of T cells by antigen-presenting cells {(APCs)} depends on the complex integration of signals that are delivered by multiple antigen receptors. Most receptor-proximal activation events in T cells were identified using multivalent anti-receptor antibodies, eliminating the need to use the more complex {APCs.} As the physiological membrane-associated ligands on the {APC} and the activating antibodies probably trigger the same biochemical pathways, it is unknown why the antibodies, even at saturating concentrations, fail to trigger some of the physiological T-cell responses. Here we study, at the level of the single cell, the responses of T cells to native ligands. We used a digital imaging system and analysed the three-dimensional distribution of receptors and intracellular proteins that cluster at the contacts between T cells and {APCs} during antigen-specific interactions. Surprisingly, instead of showing uniform oligomerization, these proteins clustered into segregated three-dimensional domains within the cell contacts. The antigen-specific formation of these new, spatially segregated supramolecular activation clusters may generate appropriate physiological responses and may explain the high sensitivity of the T cells to antigen.

D. R. Critchley, A. R. Gingras (2008): Talin at a glance
Type: article by Journal of Cell Science.
doi: 10.1242/jcs.018085
link: http://www.ncbi.nlm.nih.gov/pubmed/18434644

M. Gunzer, A. Schäfer, S. Borgmann, S. Grabbe, K. S. Zänker, E. B. Bröcker, E. Kämpgen, P. Friedl (2000): Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential
Type: article by Immunity.
link: http://www.ncbi.nlm.nih.gov/pubmed/11021530
Abstract:

Cognate interactions of naive T cells with antigen-presenting dendritic cells require physical cell-cell contacts leading to signal induction and T cell activation. Using a three-dimensional collagen matrix videomicroscopy model for ovalbumin peptide-specific activation of murine and oxidative mitogenesis of human T cells, we show that T cells maintain vigorous migration upon cognate interactions to {DC} (dendritic cell), continuously crawl across the {DC} surface, and rapidly detach (median within 6-12 min). These dynamic and short-lived encounters favor sequential contacts with the same or other {DC} and trigger calcium influx, upregulation of activation markers, T blast formation, and proliferation. We conclude that a tissue environment supports the accumulation of sequential signals, implicating a numeric or "digital" control mechanism for an ongoing primary immune response.

C. S. Shelley, N. Da Silva, J. M. Teodoridis (2001): During U937 monocytic differentiation repression of the {CD43} gene promoter is mediated by the single-stranded {DNA} binding protein Pur alpha
Type: article by British Journal of Haematology.
link: http://www.ncbi.nlm.nih.gov/pubmed/11722429
Abstract:

Human {CD43} is an abundant, heavily glycosylated molecule expressed exclusively on the surface of leucocytes. When leucocytes are at rest, {CD43} acts to prevent intercellular interaction but during leucocyte differentiation such cell-cell interaction is facilitated by {CD43.} This change in the function of {CD43} is mediated in part by a reduction in its level of expression. Previous studies have implicated proteolytic cleavage events at the cell surface in causing such reduction. Here, we report that, in an in vitro model of leucocyte differentiation, {CD43} {mRNA} levels were also subject to reduction. Specifically, we demonstrated that within 48 h of the cell line U937 being induced to differentiate along the monocytic pathway, {CD43} {mRNA} levels were reduced by 69%. This decline coincided with a decrease in the activity of the {CD43} gene promoter mediated by the single-stranded {DNA} binding protein Pur alpha. Previously, we have demonstrated that Pur alpha mediates induction of the {CD11c} beta 2 integrin promoter during U937 differentiation. Consequently, Pur alpha represents a potential means by which the induction of pro-adhesive molecules and the repression of anti-adhesive molecules is co-ordinated during leucocyte differentiation.

S. Komura, D. Andelman (2000): Adhesion-induced lateral phase separation in membranes
Type: article by The European Physical Journal E.

Z. Guttenberg, B. Lorz, E. Sackmann, A. Boulbitch (2001): First-order transition between adhesion states in a system mimicking cell-tissue interaction
Type: article by Europhysics Letters.
link: http://adsabs.harvard.edu/abs/2001EL.....54..826G
Abstract:

We establish a model of cell-tissue interaction consisting of vesicles

carrying lipopolymers (to mimic the glycocalix) and mobile specific ligands of the blood platelet integrin {alphaIIbbeta3} covering the substrate. We find the phase diagram with a first-order transition between a gravity-controlled weak state of the vesicle-substrate adhesion and a strong-adhesion state governed by receptor-ligand interaction. Adhesion energy ɛadh is measured as a function of ligand and repeller concentration by interferometric contour analysis on the basis of a new refined model of soft shell adhesion (accounting for the membrane bending and stretching at the adhesion rim of the ellipsoidal vesicle). At ligand densities comparable to integrin density, ɛadh decreases sharply. Increasing the repeller content weakens the adhesion strength.

J. W. Cahn (1977): Critical point wetting
Type: article by The Journal of Chemical Physics.
doi: 10.1063/1.434402
link: http://link.aip.org/link/?JCP/66/3667/1

U. Seifert, R. Lipowsky (1995): Morphology of vesicles
Type: article by Handbook of biological physics.

M. L. Dustin, D. R. Colman (2002): Neural and Immunological Synaptic Relations
Type: article by Science.
doi: 10.1126/science.1076386
link: http://www.sciencemag.org/cgi/content/abstract/298/5594/785

K. Choudhuri, D. Wiseman, M. H. Brown, K. Gould, P. A. van der Merwe (2005): T-cell receptor triggering is critically dependent on the dimensions of its {peptide-MHC} ligand
Type: article by Nature.
doi: 10.1038/nature03843
link: http://dx.doi.org/10.1038/nature03843

T. H. Watts, H. E. Gaub, H. M. McConnell (1986): T-cell-mediated association of peptide antigen and major histocompatibility complex protein detected by energy transfer in an evanescent wave-field
Type: article by Nature.
doi: 10.1038/320179a0
link: http://dx.doi.org/10.1038/320179a0

A. Lambacher, P. Fromherz (1996): Fluorescence interference-contrast microscopy on oxidized silicon using a monomolecular dye layer
Type: article by Applied Physics A: Materials Science & Processing.
doi: 10.1007/BF01567871
link: http://dx.doi.org/10.1007/BF01567871
Abstract:

A silicon chip is covered by a monomolecular film of a fluorescence dye with silicon dioxide used as a spacer. The fluorescence depends on the distance of the dye from the silicon. The modulation of the intensity is described quantitatively by an optical theory which accounts for interference of the exciting light and of the emitted light. The effect is used to obtain a microscopic picture of the surface profile with a precision of a few Angströms. The perspectives for an application in wet systems such as neuron-silicon junctions and lipid membranes on silicon are pointed out.

D. Zagury, J. Bernard, N. Thierness, M. Feldman, G. Berke (1975): Isolation and characterization of individual functionally reactive cytotoxic T lymphocytes: conjugation, killing and recycling at the single cell level
Type: article by European Journal of Immunology.
doi: 10.1002/eji.1830051205
link: http://dx.doi.org/10.1002/eji.1830051205
Abstract:

Isolation and characterization of individual functionally reactive cytotoxic T lymphocytes have been achieved. Peritoneal exudate cytotoxic lymphocytes were obtained from {BALB/c} mice injected with {EL4} tumor cells. Lymphocyte tumor cell conjugation was promoted by centrifugation. Individual conjugates comprised of one lymphocyte bound to one tumor cell were isolated with a micropipette. The ultrastructure of isolated killer lymphocytes and the lysis of conjugated target cells were analyzed. The cytotoxic lymphocytes are small cells with an indented nucleus which is poor in peripheral chromatin and rich in rough nuclear sap. The cytoplasm contains one-membrane-bound lysosome-like granules and clusters of ribosomes, but no rough endoplasmatic reticulum. The Golgi apparatus is well developed. Direct evidence obtained at the single cell level shows that a single effector lymphocyte is required and sufficient for the destruction of a single target cell and that killer cells which have been responsible for the lysis of a given target cell can lyse a second and even a third time.

S. Goennenwein, M. Tanaka, B. Hu, L. Moroder, E. Sackmann (2003): Functional Incorporation of Integrins into Solid Supported Membranes on Ultrathin Films of Cellulose: Impact on Adhesion
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(03)74508-1
link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B94RW-4V3HBYS-25&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1141953342&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=33cb6abafea45cb036f47a843290fa9e

Kapitel 14

R. H. Adrian (1956): The effect of internal and external potassium concentration on the membrane potential of frog muscle
Type: article by The Journal of Physiology.
link: http://www.ncbi.nlm.nih.gov/pubmed/13368111

P. C. Hiemenz, R. Rajagopalan (1997): Principles of Colloid and Surface Chemistry
Type: book by Marcel Dekker Inc.

E. Neher, B. Sakmann (1976): Single-channel currents recorded from membrane of denervated frog muscle fibres
Type: article by Nature.
link: http://www.ncbi.nlm.nih.gov/pubmed/1083489

J. Nicholls (2001): From Neuron to Brain: A Cellular and Molecular Approach to the Function of the Nervous System
Type: book by Palgrave Macmillan.

A. L. Hodgkin, A. F. Huxley (1952): Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo
Type: article by The Journal of Physiology.
link: http://www.ncbi.nlm.nih.gov/pubmed/14946713

J. Jäckle (2007): The causal theory of the resting potential of cells
Type: article by Journal of Theoretical Biology.
doi: 10.1016/j.jtbi.2007.07.027
link: http://www.ncbi.nlm.nih.gov/pubmed/17904583
Abstract:

In this pedagogical article the causal theory of the resting potential of cells is presented, which for given extracellular ion concentrations predicts the intracellular ones simultaneously with the resting potential. In addition to the Na, K-pump, fixed charges on the membrane surfaces are taken into account. The equation determining the resting potential in the causal theory suggests a new explanation of the genesis of the resting potential. The usual criterion for an ion pump to be electrogenic is not relevant for the whole of the resting potential, and may therefore be misleading. The physical meaning of the {Goldman-Hodgkin-Katz} formula for the membrane potential as a diffusion potential is also explained and tested with numbers for the giant axon of the squid. A significant discrepancy between theory and experiment is found which calls for an experimental re-examination of the constitutive equations for passive potassium and sodium currents.

R. F. Rakowski, D. C. Gadsby, P. De Weer (1989): Stoichiometry and voltage dependence of the sodium pump in voltage-clamped, internally dialyzed squid giant axon
Type: article by The Journal of General Physiology.
link: http://www.ncbi.nlm.nih.gov/pubmed/2544655
Abstract:

The stoichiometry and voltage dependence of the {Na/K} pump were studied in internally dialyzed, voltage-clamped squid giant axons by simultaneously measuring, at various membrane potentials, the changes in Na efflux (delta phi Na) and holding current (delta I) induced by dihydrodigitoxigenin {(H2DTG).} {H2DTG} stops the {Na/K} pump without directly affecting other current pathways: (a) it causes no delta I when the pump lacks Na, K, Mg, or {ATP,} and (b) ouabain causes no delta I or delta phi Na in the presence of saturating {H2DTG.} External K {(Ko)} activates Na efflux with {Michaelis-Menten} kinetics {(Km} = 0.45 +/- 0.06 {mM} {[SEM])} in Na-free seawater {(SW),} but with sigmoid kinetics in approximately 400 {mM} Na {SW} {(Hill} coefficient = 1.53 +/- 0.08, K1/2 = 3.92 +/- 0.29 {mM).} {H2DTG} inhibits less strongly {(Ki} = 6.1 +/- 0.3 {microM)} in 1 or 10 {mM} K Na-free {SW} than in 10 {mM} K, 390 {mM} Na {SW} (1.8 +/- 0.2 {microM).} Dialysis with 5 {mM} each {ATP,} phosphoenolpyruvate, and phosphoarginine reduced {Na/Na} exchange to at most 2% of the {H2DTG-sensitive} Na efflux. {H2DTG} sensitive but nonpump current caused by periaxonal K accumulation upon stopping the pump, was minimized by the K channel blockers 3,4-diaminopyridine (1 {mM),} tetraethylammonium (approximately 200 {mM),} and phenylpropyltriethylammonium (20-25 {mM)} whose adequacy was tested by varying {[K]o} (0-10 {mM)} with {H2DTG} present. Two ancillary clamp circuits suppressed stray current from the axon ends. Current and flux measured from the center pool derive from the same membrane area since, over the voltage range -60 to +20 {mV,} tetrodotoxin-sensitive current and Na efflux into Na-free {SW,} under K-free conditions, were equal. The stoichiometry and voltage dependence of pump {Na/K} exchange were examined at near-saturating {[ATP],} {[K]o} and {[Na]i} in both Na-free and 390 {mM} Na {SW.} The {H2DTG-sensitive} F delta phi Na/delta I ratio {(F} is Faraday's constant) of paired measurements corrected for membrane area match, was 2.86 +/- 0.09 (n = 8) at 0 {mV} and 3.05 +/- 0.13 (n = 6) at -60 to -90 {mV} in Na-free {SW,} and 2.72 +/- 0.09 (n = 7) at 0 {mV} and 2.91 +/- 0.21 (n = 4) at -60 {mV} in 390 {mM} Na {SW.} Its overall mean value was 2.87 +/- 0.07 (n = 25), which was not significantly different from the 3.0 expected of a 3 Na/2 K {pump.(ABSTRACT} {TRUNCATED} {AT} 400 {WORDS)}

A. L. Hodgkin, R. D. Keynes (1955): The potassium permeability of a giant nerve fibre
Type: article by The Journal of Physiology.
link: http://www.ncbi.nlm.nih.gov/pubmed/14368575

A. L. Hodgkin, A. F. Huxley (1952): A quantitative description of ion currents and its applications to conduction and excitation in nerve membranes
Type: article by The Journal of Physiology.

D. E. Goldman (1943): {POTENTIAL,} {IMPEDANCE,} {AND} {RECTIFICATION} {IN} {MEMBRANES}
Type: article by The Journal of General Physiology.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2142582&rendertype=abstract
Abstract:

Impedance and potential measurements have been made on a number of artificial membranes. Impedance changes were determined as functions of current and of the composition of the environmental solutions. It was shown that rectification is present in asymmetrical systems and that it increases with the membrane potential. The behavior in pairs of solutions of the same salt at different concentrations has formed the basis for the studies although a few experiments with different salts at the same concentrations gave results consistent with the conclusions drawn. A theoretical picture has been presented based on the use of the general kinetic equations for ion motion under the influence of diffusion and electrical forces and on a consideration of possible membrane structures. The equations have been solved for two very simple cases; one based on the assumption of microscopic electroneutrality, and the other on the assumption of a constant electric field. The latter was found to give better results than the former in interpreting the data on potentials and rectification, showing agreement, however, of the right order of magnitude only. Although the indications are that a careful treatment of boundary conditions may result in better agreement with experiment, no attempt has been made to carry this through since the data now available are not sufficiently complete or reproducible. Applications of the second theoretical case to the squid giant axon have been made showing qualitative agreement with the rectification properties and very good agreement with the membrane potential data.

R. F. Schmidt, G. Thews, F. Lang (2000): Physiologie des Menschen
Type: book by Springer Berlin.

L. J. Mullins, K. Noda (1963): The Influence of {Sodium-Free} Solution on the membrane potential of frog muscle fibers
Type: article by The Journal of General Physiology.
link: http://www.ncbi.nlm.nih.gov/pubmed/14060441

R. F. Thompson, M. Behncke Das Gehirn: Von der Nervenzelle zur Verhaltenssteuerung
Type: book by Spektrum Akademischer Verl..

A. L. Hodgkin, B. Katz (1949): The effect of sodium ions on the electrical activity of the giant axon of the squid
Type: article by The Journal of Physiology.
link: http://www.ncbi.nlm.nih.gov/pubmed/16991839

Kapitel 15

P. Mueller, D. O. Rudin, H. T. Tien, W. C. WESCOTT (1962): Reconstitution of cell membrane structure in vitro and its transformation into an excitable system
Type: article by Nature.
link: http://www.ncbi.nlm.nih.gov/pubmed/14476933

L. C. Timpe, T. L. Schwarz, B. L. Tempel, D. M. Papazian, Y. N. Jan, L. Y. Jan (1988): Expression of functional potassium channels from Shaker {cDNA} in Xenopus oocytes
Type: article by Nature.
doi: 10.1038/331143a0
link: http://www.ncbi.nlm.nih.gov/pubmed/2448636
Abstract:

The Shaker gene of Drosophila melanogaster encodes a potassium-selective ion channel, the {'A'} channel, or one of its subunits. A single Shaker messenger {RNA} species suffices to direct the synthesis of functional A channels in Xenopus oocytes. Physiological characteristics of the A currents induced by two different {mRNA} species are compared.

E. Neher, B. Sakmann (1976): Single-channel currents recorded from membrane of denervated frog muscle fibres
Type: article by Nature.
link: http://www.ncbi.nlm.nih.gov/pubmed/1083489

E. Bamberg, P. Läuger (1973): Channel formation kinetics of gramicidin A in lipid bilayer membranes
Type: article by The Journal of Membrane Biology.
link: http://www.ncbi.nlm.nih.gov/pubmed/4131309

S. B. Hladky, D. A. Haydon (1972): Ion transfer across lipid membranes in the presence of gramicidin A. I. Studies of the unit conductance channel
Type: article by Biochimica Et Biophysica Acta.
link: http://www.ncbi.nlm.nih.gov/pubmed/5048999

J. Nicholls (2001): From Neuron to Brain: A Cellular and Molecular Approach to the Function of the Nervous System
Type: book by Palgrave Macmillan.

E. Neher, C. F. Stevens (1977): Conductance fluctuations and ionic pores in membranes
Type: article by Annual Review of Biophysics and Bioengineering.
doi: 10.1146/annurev.bb.06.060177.002021
link: http://www.ncbi.nlm.nih.gov/pubmed/68708

A. L. Hodgkin, A. F. Huxley (1952): Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo
Type: article by The Journal of Physiology.
link: http://www.ncbi.nlm.nih.gov/pubmed/14946713

P. Fromherz (2001): Interfacing von Nervenzellen und Halbleiterchips
Type: article by Physikalische Blätter.

D. Colquhoun, B. Sakmann (1985): Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate
Type: article by The Journal of Physiology.
link: http://www.ncbi.nlm.nih.gov/pubmed/2419552
Abstract:

The fine structure of ion-channel activations by junctional nicotinic receptors in adult frog muscle fibres has been investigated. The agonists used were acetylcholine {(ACh),} carbachol {(CCh),} suberyldicholine {(SubCh)} and decan-1,10-dicarboxylic acid dicholine ester {(DecCh).} Individual activations (bursts) were interrupted by short closed periods; the distribution of their durations showed a major fast component ('short gaps') and a minor slower component ('intermediate gaps'). The mean duration of both short and intermediate gaps was dependent on the nature of the agonist. For short gaps the mean durations (microseconds) were: {ACh,} 20; {SubCh,} 43; {DecCh,} 71; {CCh,} 13. The mean number of short gaps per burst were: {ACh,} 1.9; {SubCh,} 4.1; {DecCh,} 2.0. The mean number of short gaps per burst, and the mean number per unit open time, were dependent on the nature of the agonist, but showed little dependence on agonist concentration or membrane potential for {ACh,} {SubCh} and {DecCh.} The short gaps in {CCh} increased in frequency with agonist concentration and were mainly produced by channel blockages by {CCh} itself. Partially open channels (subconductance states) were clearly resolved rarely (0.4% of gaps within bursts) but regularly. Conductances of 18% (most commonly) and 71% of the main value were found. However, most short gaps were probably full closures. The distribution of burst lengths had two components. The faster component represented mainly isolated short openings that were much more common at low agonist concentrations. The slower component represented bursts of longer openings. Except at very low concentrations more than 85% of activations were of this type, which corresponds to the 'channel lifetime' found by noise analysis. The frequency of channel openings increased slightly with hyperpolarization. The short gaps during activations were little affected when (a) the {[H+]o} or {[Ca2+]o} were reduced to 1/10th of normal, (b) when extracellular Ca2+ was replaced by Mg2+, (c) when the {[Cl-]i} was raised or (d) when, in one experiment on an isolated inside-out patch, the normal intracellular constituents were replaced by {KCl.} Reduction of {[Ca2+]O} to 1/10 of normal increased the single-channel conductance by 50%, and considerably increased the number of intermediate gaps. No temporal asymmetry was detectable in the bursts of openings. Positive correlations were found between the lengths of successive apparent open times at low {SubCh} concentrations, but no correlations between burst lengths were detectable. The component of brief openings behaves, at low concentrations, as though it originates from openings of singly occupied {channels.(ABSTRACT} {TRUNCATED} {AT} 400 {WORDS)}

F. Conti, E. Wanke (1975): Channel noise in nerve membranes and lipid bilayers
Type: article by Quarterly Reviews of Biophysics.
link: http://www.ncbi.nlm.nih.gov/pubmed/769042

J.-P. Changeux, J. Thiéry, Y. Tung, C. Kittel (1967): {ON} {THE} {COOPERATIVITY} {OF} {BIOLOGICAL} {MEMBRANES}
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
link: http://www.ncbi.nlm.nih.gov/pubmed/16591474

R. B. Rogart, L. L. Cribbs, L. K. Muglia, D. D. Kephart, M. W. Kaiser (1989): Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+ channel isoform
Type: article by Proceedings of the National Academy of Sciences of the United States of America.
doi: VL - 86
link: http://www.pnas.org/content/86/20/8170.abstract
Abstract:

Voltage-gated Na+ channels in mammalian heart differ from those in nerve and skeletal muscle. One major difference is that tetrodotoxin {(TTX)-resistant} cardiac Na+ channels are blocked by 1-10 {microM} {TTX,} whereas {TTX-sensitive} nerve Na+ channels are blocked by nanomolar {TTX} concentrations. We constructed a {cDNA} library from 6-day-old rat hearts, where only low-affinity {[3H]saxitoxin} receptors, corresponding to {TTX-resistant} Na+ channels, were detected. We isolated several overlapping {cDNA} clones encompassing 7542 nucleotides and encoding the entire alpha subunit of a cardiac-specific Na+ channel isoform (designated rat heart I) as well as several rat brain I Na+ channel {cDNA} clones. The derived amino acid sequence of rat heart I was highly homologous to, but distinct from, previous Na+ channel clones. {RNase} protection studies showed that the corresponding {mRNA} species is abundant in newborn and adult rat hearts, but not detectable in brain or innervated skeletal muscle. The same {mRNA} species appears upon denervation of skeletal muscle, likely accounting for expression of new {TTX-resistant} Na+ channels. Thus, this cardiac-specific Na+ channel clone appears to encode a distinct {TTX-resistant} isoform and is another member of the mammalian Na+ channel multigene family, found in newborn heart and denervated skeletal muscles.

F. J. Sigworth, E. Neher (1980): Single Na+ channel currents observed in cultured rat muscle cells
Type: article by Nature.
link: http://www.ncbi.nlm.nih.gov/pubmed/6253802
Abstract:

The voltage- and time-dependent conductance of membrane Na+ channels is responsible for the propagation of action potentials in nerve and muscle cells. In voltage-step-clamp experiments on neurone preparations containing 10(4)-10(7) Na+ channels the membrane conductance shows smooth variations in time, but analysis of fluctuations and other eivdence suggest that the underlying single-channel conductance changes are stochastic, rapid transitions between 'closed' and 'open' states as seen in other channel types. We report here the first observations of currents through individual Na+ channels under physiological conditions using an improved version of the extracellular patch-clamp technique on cultured rat muscle cells. Our observations support earlier inferences about channel gating and show a single-channel conductance of approximately 18 {pS.}

C. M. Armstrong, F. Bezanilla (1977): Inactivation of the sodium channel. {II.} Gating current experiments
Type: article by The Journal of General Physiology.
link: http://www.ncbi.nlm.nih.gov/pubmed/591912
Abstract:

Gating current {(Ig)} has been studied in relation to inactivation of Na channels. No component of Ig has the time course of inactivation; apparently little or no charge movement is associated with this step. Inactivation nonetheless affects Ig by immobilizing about two-thirds of gating charge. Immobilization can be followed by measuring {ON} charge movement during a pulse and comparing it to {OFF} charge after the pulse. The {OFF:ON} ratio is near 1 for a pulse so short that no inactivation occurs, and the ratio drops to about one-third with a time course that parallels inactivation. Other correlations between inactivation and immobilization are that: (a) they have the same voltage dependence; (b) charge movement recovers with the time coures of recovery from inactivation. We interpret this to mean that the immobilized charge returns slowly to "off" position with the time course of recovery from inactivation, and that the small current generated is lost in base-line noise. At -150 {mV} recover is very rapid, and the immobilized charge forms a distinct slow component of current as it returns to off position. After destruction of inactivation by pronase, there is no immobilization of charge. A model is presented in which inactivation gains its voltage dependence by coupling to the activation gate.

H. M. Fishman, H. R. Leuchtag, L. E. Moore (1983): Fluctuation and linear analysis of Na-current kinetics in squid axon
Type: article by Biophysical Journal.
doi: 10.1016/S0006-3495(83)84353-7
link: http://www.ncbi.nlm.nih.gov/pubmed/6626670
Abstract:

The power spectrum of current fluctuations and the complex admittance of squid axon were determined in the frequency range 12.5 to 5,000 Hx during membrane voltage clamps to the same potentials in the same axon during internal perfusion with cesium. The complex admittance was determined rapidly and with high resolution by a fast Fourier transform computation of the current response, acquired after a steady state was attained, to a synthesized signal with predetermined spectral characteristics superposed as a continuous, repetitive, small perturbation on step voltage clamps. Linear conduction parameters were estimated directly from admittance data by fitting an admittance model, derived from the linearized {Hodgkin-Huxley} equations modified by replacing the membrane capacitance with a "constant-phase-angle" capacitance, to the data. The constant phase angle obtained was approximately 80 degrees. At depolarizations the phase of the admittance was 180 degrees, and the real part of the impedance locus was in the left-half complex plane for frequencies below 1 {kHz,} which indicates a steady-state negative Na conductance. The fits also yielded estimates of the natural frequencies of Na "activation" and "inactivation" processes. By fitting Na-current noise spectra with a double Lorentzian function, a lower and an upper corner frequency were obtained; these were compared with the two natural frequencies determined from admittance analysis at the corresponding potentials. The frequencies from fluctuation analyses ranged from 1.0 to 10.3 times higher than those from linear (admittance) analysis. This discrepancy is consistent with the concept that the fluctuations reflect a nonlinear rate process that cannot be fully characterized by linear perturbation analysis. Comparison of the real part of the admittance and the current noise spectrum shows that the Nyquist relation, which generally applies to equilibrium conductors, does not hold for the Na process in squid axon. The Na-channel conductance, gamma Na, was found to increase monotonically from 0.1 to 4.8 {pS} for depolarizations up to 50 {mV} from a holding potential of -60 {mV,} with no indication of a maximum value.

J. M. Berg, L. Stryer, J. L. Tymoczko (2007): Biochemie
Type: book by Spektrum Akademischer Verlag.

N. Unwin (2005): Refined structure of the nicotinic acetylcholine receptor at {4A} resolution
Type: article by Journal of Molecular Biology.
doi: 10.1016/j.jmb.2004.12.031
link: http://www.ncbi.nlm.nih.gov/pubmed/15701510
Abstract:

We present a refined model of the membrane-associated Torpedo acetylcholine {(ACh)} receptor at {4A} resolution. An improved experimental density map was obtained from 342 electron images of helical tubes, and the refined structure was derived to an R-factor of 36.7% {(R(free)} 37.9%) by standard crystallographic methods, after placing the densities corresponding to a single molecule into an artificial unit cell. The agreement between experimental and calculated phases along the helical layer-lines was used to monitor progress in the refinement and to give an independent measure of the accuracy. The atomic model allowed a detailed description of the whole receptor in the closed-channel form, including the ligand-binding and intracellular domains, which have not previously been interpreted at a chemical level. We confirm that the two ligand-binding alpha subunits have a different extended conformation from the three other subunits in the closed channel, and identify several interactions on both pairs of subunit interfaces, and within the alpha subunits, which may be responsible for their "distorted" structures. The {ACh-coordinating} amino acid side-chains of the alpha subunits are far apart in the closed channel, indicating that a localised rearrangement, involving closure of loops B and C around the bound {ACh} molecule, occurs upon activation. A comparison of the structure of the alpha subunit with that of {AChBP} having ligand present, suggests how the localised rearrangement overcomes the distortions and initiates the rotational movements associated with opening of the channel. Both vestibules of the channel are strongly electronegative, providing a cation-stabilising environment at either entrance of the membrane pore. Access to the pore on the intracellular side is further influenced by narrow lateral windows, which would be expected to screen out electrostatically ions of the wrong charge and size.

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