The Fluid Mosaic Model of Membrane Structure

  • S. J. Singer
Part of the Nobel Foundation Symposia book series (NOFS, volume 34)


The fluid mosaic model had its origins in an analysis of the equilibrium thermodynamics of membrane systems, which led to the suggestion that the integral proteins of membranes are amphipathic molecules. This thermodynamic analysis continues to have considerable explanatory and predictive power for problems of membrane structure and function. In this paper, the analysis is applied to explain or predict the relatively hydrophobic amino acid composition of integral proteins, their large content of a-helical secondary structure, the characteristics of the short-range interactions of lipids and integral proteins, the molecular asymmetry of the integral proteins and phospholipids of membranes, the possible biogenesis of such asymmetry, and the mechanisms of transport of small ionic and polar molecules through membranes.


Membrane Structure Polar Head Group Hydrophilic Interaction Integral Protein Human Erythrocyte Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bloj, B. and D. B. Zilversmit, Asymmetry and transposition rate of phosphatidylcholine in rat erythrocyte membranes, Biochemistry 15, 1277, 1976.PubMedCrossRefGoogle Scholar
  2. Bretscher, M. S., Phosphatidyl-ethanolamine: differential labelling in intact cells and cell ghosts of human erythrocytes by a membrane-impermeable reagent, J. Mol. Biol. 71, 523, 1972.PubMedCrossRefGoogle Scholar
  3. Bretscher, M. S., Membrane Structure: Some general principles, Science 181, 622, 1973.PubMedCrossRefGoogle Scholar
  4. Cabantchik, Z. I. and A. Rothstein, Membrane proteins related to anion permeability of human red blood cells. I. Localization of disulfonic stilbene binding sites in proteins involved in permeation, J. Membrane Biol. 15, 207, 1974.CrossRefGoogle Scholar
  5. Capaldi, R. A. and G. Vanderkooi, The low polarity of many membrane proteins, Proc. Nat. Acad. Sci. U.S.A. 69, 930, 1972.CrossRefGoogle Scholar
  6. Cohn, E. J. and J. T. Edsall,Proteins, Amino Acids and Peptides, p. 201, Reinhold Publ. Co., New York, 1943.Google Scholar
  7. Dutton, A., E. D. Rees and S. J. Singer, An experiment eliminating the rotating carrier mechanism for the active transport of Ca ion in sarcoplasmic reticulum membranes, Proc. Nat. Acad. Sci. U.S.A. 73, 0000, 1976.CrossRefGoogle Scholar
  8. Edsall, J. T. and J. Wyman, Biophysical Chemistry, p. 258, Academic Press, New York, 1958.Google Scholar
  9. Gordesky, S. E., G. V. Marinetti and R. J. Love, The reaction of chemical probes with the erythrocyte membrane, J. Membrane Biol. 20, 111, 1975.CrossRefGoogle Scholar
  10. Henderson, R. and P. N. T. Unwin, Three-dimensional model of purple membrane obtained by electron microscopy, Nature (Lond.) 257, 28, 1975.CrossRefGoogle Scholar
  11. Hill, E., D. Tsernoglou, L. Webb and L. J. Banaszak, Polypeptide conformation of cytoplasmic malate dehydrogenase from an electron density map at 3.0 A resolution, J. Mol. Biol. 72, 577, 1972.PubMedCrossRefGoogle Scholar
  12. Hirano, H., B. Parkhouse,G. L. Nicolson,E. S. Lennox and S. J. Singer, Distribution of saccharide residues on membrane fragments from a myeloma-cell homogenate: its implications for membrane biogenesis, Proc. Nat. Acad. Sci. U.S.A. 69, 2945, 1972.CrossRefGoogle Scholar
  13. Jardetzky, 0., Simple allosteric model for membrane pumps. Nature (Lond.) 211, 969, 1966.CrossRefGoogle Scholar
  14. Jost, P. C., 0. H. Griffith, R. A. Capaldi and G. Vanderkooi, Evi-dence for boundary lipid in membranes, Proc. Nat. Acad. Sci. U.S.A. 70, 480, 1973.CrossRefGoogle Scholar
  15. Kauzmann, W., Some factors in the interpretation of protein denaturation, Advances Protein Chem. 14, 1, 1959.PubMedCrossRefGoogle Scholar
  16. Klotz, I. M. and S. B. Farnham, Stability of an amide-hydrogen bond in an apolar environment, Biochemistry 7, 3879, 1968.PubMedCrossRefGoogle Scholar
  17. Klotz, I. M. and J. S. Franzen, Hydrogen bonds between model peptide groups in solution, J. Amer. Chem. Soc. 84, 3461, 1962.CrossRefGoogle Scholar
  18. Kornberg, R. D. and H. M. McConnell, Inside-outside transitions of phospholipids in vesicle membranes, Biochemistry 10, 1111, 1971.PubMedCrossRefGoogle Scholar
  19. Kyte, J., The reactions of sodium and potassium ion-activated aden-osine triphosphatase with specific antibodies. Implications for the mechanism of active transport, J. Biol. Chem. 249, 3652, 1974.PubMedGoogle Scholar
  20. Kyte, J., Structural studies of sodium and potassium ion-activated adenosine triphosphatase. The relationship between molecular structure and the mechanism of active transport. J. Biol. Chem. 250, 7443, 1975.PubMedGoogle Scholar
  21. Lenard, J. and S. J. Singer, Protein conformation in cell membrane preparations as studied by optical rotatory dispersion and circular dichroism, Proc. Nat. Acad. Sci. U.S.A. 56, 1828, 1966.CrossRefGoogle Scholar
  22. Martinosi, A. and F. Fortier, The effect of anti-ATPase antibodies upon the Ca+ transport of sarcoplasmic reticulum, Biochem. Biophys. Res. Commun. 60, 382, 1974.CrossRefGoogle Scholar
  23. Matthews, F. S.t. P. Argos and M. Levine, The structure of cytochrome b5 at 2.0 A resolution, Cold Spring Harbor Symp. Quant. Biol. 36, 387, 1972.CrossRefGoogle Scholar
  24. McNamee, M. G. and H. M. McConnell, Transmembrane potentials and phospholipid flip-flop in excitable membrane vesicles, Biochemistry 12, 2951, 1973.PubMedCrossRefGoogle Scholar
  25. Nicolson, G. L. and S. J. Singer, Ferritin-conjugated plant agglutinins as specific saccharide stains for electron microscopy: application to saccharides bound to cell membranes. Proc. Nat. Acad. Sci. U.S.A. 68, 942, 1971.CrossRefGoogle Scholar
  26. Nicolson, G. L. and S. J. Singer, The distribution and asymmetry of mammalian cell surface saccharides utilizing ferritin-conjugated plant agglutinins as specific saccharide stains, J. Cell Biol. 60, 236, 1974.PubMedCrossRefGoogle Scholar
  27. Renooij, W., L. M. Van Golde, R. F. A. Zwaal and L. L. M. Van Deenan, Topological asymmetry of phospholipid metabolism in rat erythrocyte membranes, Eur. J. Biochem. 61, 53, 1976.PubMedCrossRefGoogle Scholar
  28. Roseman, M., B. J. Litman and T. E. Thompson, Transbilayer exchange of phosphatidylethanolamine for phosphatidylcholine and Nacetimidoylphosphatidylethanolamine in single-walled bilayer vesicles, Biochemistry 14, 4826, 1975.PubMedCrossRefGoogle Scholar
  29. Rothman, J. E., D. K. Tsai, E. A. Dawidowicz and J. Lenard, Transbilayer phospholipid asymmetry and its maintenance in the membrane of influenza virus, Biochemistry, in press, 1976.Google Scholar
  30. Ruoho, A. and J. Kyte Photoaffinity labeling of the ouabain-binding site on (Na+ + KT) adenosinetriphosphatase, Proc. Nat. Acad. Sci. U.S.A. 71, 2352, 1974.CrossRefGoogle Scholar
  31. Segrest, J. P., I. Kahane, R. L. Jackson and V. T. Marchesi, Major glycoprotein of the human erythrocyte membrane. Evidence for an amphipathic molecular structure, Arch. Biochem. Biophys. 155, 167, 1973.PubMedCrossRefGoogle Scholar
  32. Segrest, J. P., T. Gulik-Krzywicki and C. Sardet, Association of the membrane-penetrating polypeptide segment of the human erythro-cyte MN-glycoprotein with phospholipid bilayers, Proc. Nat. Acad. Sci. U.S.A. 71, 3294, 1974.CrossRefGoogle Scholar
  33. Singer, S. J., The molecular organization of biological membranes, in Structure and Function of Biological Membranes, pp. 145–222, edited by L. I. Rothman, Academic Press, New York, 1971.Google Scholar
  34. Singer, S. J., The molecular organization of membranes, Ann. Rev. Biochem. 43, 805, 1974.PubMedCrossRefGoogle Scholar
  35. Singer, S. J. and G. L. Nicolson, The fluid mosaic model of the structure of cell membranes, Science 175, 720, 1972.PubMedCrossRefGoogle Scholar
  36. Skou, J. C., Further investigations on a Mg— + Nat-activated aden-osinetriphosphatase, possibly related to the active, linked transport of Na+ and K+ across the nerve membrane, Biochim. Biophys. Acta 42, 6, 1960.CrossRefGoogle Scholar
  37. Spatz, L. and P. Strittmatter, A form of reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase containing both the catalytic site and an additional hydrophobic membrane-binding segment, J. Biol. Chem. 248, 793, 1973.PubMedGoogle Scholar
  38. Strittmatter, P., M. J. Rogers and L. Spatz, The binding of cyto-chrome b5 to liver microsomes, J. Biol. Chem. 247, 7188, 1972.PubMedGoogle Scholar
  39. Tanford, C., The association of acetate with ammonium and guanidinuimions., J. Amer. Chem. Soc. 76, 945, 1954.CrossRefGoogle Scholar
  40. Tsai, K.-H. and J. Lenard, Asymmetry of influenza virus membrane bi-layer demonstrated with phospholipase-C, Nature (Lond.) 253, 554, 1975.CrossRefGoogle Scholar
  41. Verkleij, A. J., R. F. A. Zwaal, B. Roelofsen, P. Comfurius, D. Kastelijn and L. L. M. Van Deenan, The asymmetric distribution of phospholipids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy, Biochim. Biophys. Acta 323, 178, 1973.PubMedCrossRefGoogle Scholar
  42. Wallach, D. F. H. and P. H. Zahler, Protein conformations in cellular membranes, Proc. Nat. Acad. Sci. U.S.A. 56, 1552, 1966.CrossRefGoogle Scholar
  43. Warren, G. B., M. D. Houslay, J. C. Metcalfe and N. J. M. Birdsall, Cholesterol is excluded from the phospholipid annulus surround-ing an active calcium transport protein, Nature (Lond.) 255, 684, 1975.CrossRefGoogle Scholar
  44. Zwaal, R. F. A., B. Roelofsen and C. M. Colley, Localization of red cell membrane constituents, Biochim. Biophys. Acta 300, 159, 1973.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • S. J. Singer
    • 1
  1. 1.Department of BiologyUniversity of California at San DiegoLa JollaUSA

Personalised recommendations