A fluid mosaic model is presented for the gross organization and structure of the proteins and lipids of biological membranes. The model is consistent with the restrictions imposed by thermodynamics. In this model, the proteins that are integral to the membrane are a heterogeneous set of globular molecules, each arranged in an amphipathic structure, that is, with the ionic and highly polar groups protruding from the membrane into the aqueous phase, and the nonpolar groups largely buried in the hydrophobic interior of the membrane. These globular molecules are partially embedded in a matrix of phospholipid. The bulk of the phospholipid is organized as a discontinuous, fluid bilayer, although a small fraction of the lipid may interact specifically with the membrane proteins. The fluid mosaic structure is therefore formally analogous to a two-dimensional oriented solution of integral proteins (or lipoproteins) in the viscous phospholipid bilayer solvent. Recent experiments with a wide variety of techniqes and several different membrane systems are described, all of which abet consistent with, and add much detail to, the fluid mosaic model. It therefore seems appropriate to suggest possible mechanisms for various membrane functions and membrane-mediated phenomena in the light of the model. As examples, experimentally testable mechanisms are suggested for cell surface changes in malignant transformation, and for cooperative effects exhibited in the interactions of membranes with some specific ligands. Note added in proof: Since this article was written, we have obtained electron microscopic evidence (69) that the concanavalin A binding sites on the membranes of SV40 virus-transformed mouse fibroblasts (3T3 cells) are more clustered than the sites on the membranes of normal cells, as predicted by the hypothesis represented in Fig. 7B. T-here has also appeared a study by Taylor et al. (70) showing the remarkable effects produced on lymphocytes by the addition of antibodies directed to their surface immunoglobulin molecules. The antibodies induce a redistribution and pinocytosis of these surface immunoglobulins, so that within about 30 minutes at 37 degrees C the surface immunoglobulins are completely swept out of the membrane. These effects do not occur, however, if the bivalent antibodies are replaced by their univalent Fab fragments or if the antibody experiments are carried out at 0 degrees C instead of 37 degrees C. These and related results strongly indicate that the bivalent antibodies produce an aggregation of the surface immunoglobulin molecules in the plane of the membrane, which can occur only if the immunoglobulin molecules are free to diffuse in the membrane. This aggregation then appears to trigger off the pinocytosis of the membrane components by some unknown mechanism. Such membrane transformations may be of crucial importance in the induction of an antibody response to an antigen, as well as iv other processes of cell differentiation.

The fluid mosaic model of the structure of cell membranes.

After infection and a prolonged incubation period, the scrapie agent causes a degenerative disease of the central nervous system in sheep and goats. Six lines of evidence including sensitivity to proteases demonstrate that this agent contains a protein that is required for infectivity. Although the scrapie agent is irreversibly inactivated by alkali, five procedures with more specificity for modifying nucleic acids failed to cause inactivation. The agent shows heterogeneity with respect to size, apparently a result of its hydrophobicity; the smallest form may have a molecular weight of 50,000 or less. Because the novel properties of the scrapie agent distinguish it from viruses, plasmids, and viroids, a new term "prion" is proposed to denote a small proteinaceous infectious particle which is resistant to inactivation by most procedures that modify nucleic acids. Knowledge of the scrapie agent structure may have significance for understanding the causes of several degenerative diseases.

http://science.sciencemag.org/content/sci/216/4542/136.full.pdf

Novel proteinaceous infectious particles cause scrapie

A historical perspective on the application of molecular dynamics (MD) to biological macromolecules is presented. Recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed us to reach the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories. We illustrate such applications on nucleic acid duplexes, RNA hairpins, protein folding trajectories, and protein−ligand, protein−protein, and protein−nucleic acid interactions.

Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models

THE FLUID MOSAIC MODEL OF THE STRUCTURE OF CELL MEMBRANES Reprinted with permission from Science, Copyright AAA, 18 February 1972, Volume 175, pp. 720–731.

The specific bonding of DNA base pairs provides the chemical foundation for genetics. This powerful molecular recognition system can be used in nanotechnology to direct the assembly of highly structured materials with specific nanoscale features, as well as in DNA computation to process complex information. The exploitation of DNA for material purposes presents a new chapter in the history of the molecule.

/pdf/dna-in-a-material-world-28gymklany.pdf

DNA in a material world

The fundamental connexion between thermoluminescence, phosphorescence and electron traps in solids has been investigated. Thermoluminescence and long-period phosphorescence arise from the release of electrons from metastable levels or traps. By studying the thermal stability of trapped electrons and the probability of release from traps of different depths, methods have been developed for finding the depths of electron traps in phosphors. The main experiment consists in exciting the phosphor at low temperatures until all the traps are filled; the phosphor is then warmed at a steady rate and the light emitted while warming is measured as a function of the temperature. The results show that the trap distribution in impurity phosphors such as willemite and the alkaline earth sulphides are, in general, complex, and extend over a range often as wide as 0·2-1·0 eV. The probability of release of an electron from a trap of depth E at temperature T is of the form se -E/kT , where is a constant. Values of s for alkaline earth and zinc sulphides are in the neighbourhood of 10 8 ±1 sec. -1 .

/pdf/phosphorescence-and-electron-traps-i-the-study-of-trap-4lf8jnxxv8.pdf

Phosphorescence and Electron Traps. I. The Study of Trap Distributions

The molecular configuration of deoxyribonucleic acid: II. Molecular models and their fourier transforms

The molecular configuration of deoxyribonucleic acid

X-ray diffraction studies show that lipid hydrocarbon chains are uniformly packed in bilayers and oriented so that their free ends are near the centre. This provides a model for biological membranes.

Structure of oriented lipid bilayers.

Diffraction analysis of dispersions of membranes makes it possible to study membranes not in regular arrays. Such analysis shows that a phospholipid bilayer is a predominant structural component of membranes with various different functions.

M. H. F. Wilkins

Papers

Phosphorescence and Electron Traps. I. The Study of Trap Distributions

The molecular configuration of deoxyribonucleic acid: II. Molecular models and their fourier transforms

The molecular configuration of deoxyribonucleic acid

Structure of oriented lipid bilayers.

Bilayer structure in membranes.