Bibliography

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

Contents 1 Kapitel 1 2 Kapitel 2 3 Kapitel 3 4 Kapitel 4 5 Kapitel 5 6 Kapitel 6 7 Kapitel 7 8 Kapitel 8 9 Kapitel 9 10 Kapitel 10

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.