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. 1999 Dec;77(6):3163–3175. doi: 10.1016/S0006-3495(99)77147-X

A model for membrane patchiness: lateral diffusion in the presence of barriers and vesicle traffic.

L A Gheber 1, M Edidin 1
PMCID: PMC1300587  PMID: 10585938

Abstract

Patches (lateral heterogeneities) of cell surface membrane proteins and lipids have been imaged by a number of different microscopy techniques. This patchiness has been taken as evidence for the organization of membranes into domains whose composition differs from the average for the entire membrane. However, the mechanism and specificity of patch formation are not understood. Here we show how vesicle traffic to and from a cell surface membrane can create patches of molecules of the size observed experimentally. Our computer model takes into account lateral diffusion, barriers to lateral diffusion, and vesicle traffic to and from the plasma membrane. Neither barriers nor vesicle traffic alone create and maintain patches. Only the combination of these produces a dynamic but persistent patchiness of membrane proteins and lipids.

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Selected References

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  1. Abney J. R., Scalettar B. A. Fluctuations and membrane heterogeneity. Biophys Chem. 1995 Dec;57(1):27–36. doi: 10.1016/0301-4622(95)00042-v. [DOI] [PubMed] [Google Scholar]
  2. Betzig E., Trautman J. K., Harris T. D., Weiner J. S., Kostelak R. L. Breaking the diffraction barrier: optical microscopy on a nanometric scale. Science. 1991 Mar 22;251(5000):1468–1470. doi: 10.1126/science.251.5000.1468. [DOI] [PubMed] [Google Scholar]
  3. Betzig E., Trautman J. K. Near-field optics: microscopy, spectroscopy, and surface modification beyond the diffraction limit. Science. 1992 Jul 10;257(5067):189–195. doi: 10.1126/science.257.5067.189. [DOI] [PubMed] [Google Scholar]
  4. Brown D. A., London E. Structure of detergent-resistant membrane domains: does phase separation occur in biological membranes? Biochem Biophys Res Commun. 1997 Nov 7;240(1):1–7. doi: 10.1006/bbrc.1997.7575. [DOI] [PubMed] [Google Scholar]
  5. Damjanovich S., Gáspár R., Jr, Pieri C. Dynamic receptor superstructures at the plasma membrane. Q Rev Biophys. 1997 Feb;30(1):67–106. doi: 10.1017/s0033583596003307. [DOI] [PubMed] [Google Scholar]
  6. Damke H., Baba T., van der Bliek A. M., Schmid S. L. Clathrin-independent pinocytosis is induced in cells overexpressing a temperature-sensitive mutant of dynamin. J Cell Biol. 1995 Oct;131(1):69–80. doi: 10.1083/jcb.131.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Denisov G., Wanaski S., Luan P., Glaser M., McLaughlin S. Binding of basic peptides to membranes produces lateral domains enriched in the acidic lipids phosphatidylserine and phosphatidylinositol 4,5-bisphosphate: an electrostatic model and experimental results. Biophys J. 1998 Feb;74(2 Pt 1):731–744. doi: 10.1016/S0006-3495(98)73998-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edidin M., Kuo S. C., Sheetz M. P. Lateral movements of membrane glycoproteins restricted by dynamic cytoplasmic barriers. Science. 1991 Nov 29;254(5036):1379–1382. doi: 10.1126/science.1835798. [DOI] [PubMed] [Google Scholar]
  9. Edidin M. Lipid microdomains in cell surface membranes. Curr Opin Struct Biol. 1997 Aug;7(4):528–532. doi: 10.1016/s0959-440x(97)80117-0. [DOI] [PubMed] [Google Scholar]
  10. Edidin M. Patches, posts and fences: proteins and plasma membrane domains. Trends Cell Biol. 1992 Dec;2(12):376–380. doi: 10.1016/0962-8924(92)90050-w. [DOI] [PubMed] [Google Scholar]
  11. Edidin M., Stroynowski I. Differences between the lateral organization of conventional and inositol phospholipid-anchored membrane proteins. A further definition of micrometer scale membrane domains. J Cell Biol. 1991 Mar;112(6):1143–1150. doi: 10.1083/jcb.112.6.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Edidin M., Zúiga M. C., Sheetz M. P. Truncation mutants define and locate cytoplasmic barriers to lateral mobility of membrane glycoproteins. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3378–3382. doi: 10.1073/pnas.91.8.3378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feder T. J., Brust-Mascher I., Slattery J. P., Baird B., Webb W. W. Constrained diffusion or immobile fraction on cell surfaces: a new interpretation. Biophys J. 1996 Jun;70(6):2767–2773. doi: 10.1016/S0006-3495(96)79846-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Holowka D., Baird B. Antigen-mediated IGE receptor aggregation and signaling: a window on cell surface structure and dynamics. Annu Rev Biophys Biomol Struct. 1996;25:79–112. doi: 10.1146/annurev.bb.25.060196.000455. [DOI] [PubMed] [Google Scholar]
  15. Hwang J., Gheber L. A., Margolis L., Edidin M. Domains in cell plasma membranes investigated by near-field scanning optical microscopy. Biophys J. 1998 May;74(5):2184–2190. doi: 10.1016/S0006-3495(98)77927-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jain M. K., White H. B., 3rd Long-range order in biomembranes. Adv Lipid Res. 1977;15:1–60. doi: 10.1016/b978-0-12-024915-2.50007-4. [DOI] [PubMed] [Google Scholar]
  17. Kusumi A., Sako Y. Cell surface organization by the membrane skeleton. Curr Opin Cell Biol. 1996 Aug;8(4):566–574. doi: 10.1016/s0955-0674(96)80036-6. [DOI] [PubMed] [Google Scholar]
  18. Monks C. R., Freiberg B. A., Kupfer H., Sciaky N., Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature. 1998 Sep 3;395(6697):82–86. doi: 10.1038/25764. [DOI] [PubMed] [Google Scholar]
  19. Peters R. Lateral mobility of proteins and lipids in the red cell membrane and the activation of adenylate cyclase by beta-adrenergic receptors. FEBS Lett. 1988 Jul 4;234(1):1–7. doi: 10.1016/0014-5793(88)81290-0. [DOI] [PubMed] [Google Scholar]
  20. Piknová B., Marsh D., Thompson T. E. Fluorescence-quenching study of percolation and compartmentalization in two-phase lipid bilayers. Biophys J. 1996 Aug;71(2):892–897. doi: 10.1016/S0006-3495(96)79291-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sabra M. C., Mouritsen O. G. Steady-state compartmentalization of lipid membranes by active proteins. Biophys J. 1998 Feb;74(2 Pt 1):745–752. doi: 10.1016/S0006-3495(98)73999-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sako Y., Kusumi A. Barriers for lateral diffusion of transferrin receptor in the plasma membrane as characterized by receptor dragging by laser tweezers: fence versus tether. J Cell Biol. 1995 Jun;129(6):1559–1574. doi: 10.1083/jcb.129.6.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Saxton M. J., Jacobson K. Single-particle tracking: applications to membrane dynamics. Annu Rev Biophys Biomol Struct. 1997;26:373–399. doi: 10.1146/annurev.biophys.26.1.373. [DOI] [PubMed] [Google Scholar]
  24. Scheiffele P., Roth M. G., Simons K. Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain. EMBO J. 1997 Sep 15;16(18):5501–5508. doi: 10.1093/emboj/16.18.5501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schnapp B. J., Gelles J., Sheetz M. P. Nanometer-scale measurements using video light microscopy. Cell Motil Cytoskeleton. 1988;10(1-2):47–53. doi: 10.1002/cm.970100109. [DOI] [PubMed] [Google Scholar]
  26. Sheets E. D., Lee G. M., Simson R., Jacobson K. Transient confinement of a glycosylphosphatidylinositol-anchored protein in the plasma membrane. Biochemistry. 1997 Oct 14;36(41):12449–12458. doi: 10.1021/bi9710939. [DOI] [PubMed] [Google Scholar]
  27. Simons K., Ikonen E. Functional rafts in cell membranes. Nature. 1997 Jun 5;387(6633):569–572. doi: 10.1038/42408. [DOI] [PubMed] [Google Scholar]
  28. Singer S. J., Nicolson G. L. The fluid mosaic model of the structure of cell membranes. Science. 1972 Feb 18;175(4023):720–731. doi: 10.1126/science.175.4023.720. [DOI] [PubMed] [Google Scholar]
  29. Stauffer T. P., Meyer T. Compartmentalized IgE receptor-mediated signal transduction in living cells. J Cell Biol. 1997 Dec 15;139(6):1447–1454. doi: 10.1083/jcb.139.6.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Steinman R. M., Mellman I. S., Muller W. A., Cohn Z. A. Endocytosis and the recycling of plasma membrane. J Cell Biol. 1983 Jan;96(1):1–27. doi: 10.1083/jcb.96.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thompson T. E., Sankaram M. B., Biltonen R. L., Marsh D., Vaz W. L. Effects of domain structure on in-plane reactions and interactions. Mol Membr Biol. 1995 Jan-Mar;12(1):157–162. doi: 10.3109/09687689509038512. [DOI] [PubMed] [Google Scholar]
  32. Yechiel E., Edidin M. Micrometer-scale domains in fibroblast plasma membranes. J Cell Biol. 1987 Aug;105(2):755–760. doi: 10.1083/jcb.105.2.755. [DOI] [PMC free article] [PubMed] [Google Scholar]

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