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. 1999 Jun;76(6):2951–2965. doi: 10.1016/S0006-3495(99)77450-3

Lipid flow through fusion pores connecting membranes of different tensions.

Y A Chizmadzhev 1, D A Kumenko 1, P I Kuzmin 1, L V Chernomordik 1, J Zimmerberg 1, F S Cohen 1
PMCID: PMC1300267  PMID: 10354423

Abstract

When two membranes fuse, their components mix; this is usually described as a purely diffusional process. However, if the membranes are under different tensions, the material will spread predominantly by convection. We use standard fluid mechanics to rigorously calculate the steady-state convective flux of lipids. A fusion pore is modeled as a toroid shape, connecting two planar membranes. Each of the membrane monolayers is considered separately as incompressible viscous media with the same shear viscosity, etas. The two monolayers interact by sliding past each other, described by an intermonolayer viscosity, etar. Combining a continuity equation with an equation that balances the work provided by the tension difference, Deltasigma, against the energy dissipated by flow in the viscous membrane, yields expressions for lipid velocity, upsilon, and area of lipid flux, Phi. These expressions for upsilon and Phi depend on Deltasigma, etas, etar, and geometrical aspects of a toroidal pore, but the general features of the theory hold for any fusion pore that has a roughly hourglass shape. These expressions are readily applicable to data from any experiments that monitor movement of lipid dye between fused membranes under different tensions. Lipid velocity increases nonlinearly from a small value for small pore radii, rp, to a saturating value at large rp. As a result of velocity saturation, the flux increases linearly with pore radius for large pores. The calculated lipid flux is in agreement with available experimental data for both large and transient fusion pores.

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Selected References

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  1. Azzi A. The application of fluorescent probes in membrane studies. Q Rev Biophys. 1975 May;8(2):237–316. doi: 10.1017/s0033583500001803. [DOI] [PubMed] [Google Scholar]
  2. Chandler D. E., Heuser J. Membrane fusion during secretion: cortical granule exocytosis in sex urchin eggs as studied by quick-freezing and freeze-fracture. J Cell Biol. 1979 Oct;83(1):91–108. doi: 10.1083/jcb.83.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chanturiya A., Chernomordik L. V., Zimmerberg J. Flickering fusion pores comparable with initial exocytotic pores occur in protein-free phospholipid bilayers. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14423–14428. doi: 10.1073/pnas.94.26.14423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen Y. D., Rubin R. J., Szabo A. Fluorescence dequenching kinetics of single cell-cell fusion complexes. Biophys J. 1993 Jul;65(1):325–333. doi: 10.1016/S0006-3495(93)81076-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chernomordik L. V., Frolov V. A., Leikina E., Bronk P., Zimmerberg J. The pathway of membrane fusion catalyzed by influenza hemagglutinin: restriction of lipids, hemifusion, and lipidic fusion pore formation. J Cell Biol. 1998 Mar 23;140(6):1369–1382. doi: 10.1083/jcb.140.6.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chernomordik L. V., Leikina E., Frolov V., Bronk P., Zimmerberg J. An early stage of membrane fusion mediated by the low pH conformation of influenza hemagglutinin depends upon membrane lipids. J Cell Biol. 1997 Jan 13;136(1):81–93. doi: 10.1083/jcb.136.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chernomordik L. V., Melikyan G. B., Chizmadzhev Y. A. Biomembrane fusion: a new concept derived from model studies using two interacting planar lipid bilayers. Biochim Biophys Acta. 1987 Oct 5;906(3):309–352. doi: 10.1016/0304-4157(87)90016-5. [DOI] [PubMed] [Google Scholar]
  8. Chernomordik L., Kozlov M. M., Zimmerberg J. Lipids in biological membrane fusion. J Membr Biol. 1995 Jul;146(1):1–14. doi: 10.1007/BF00232676. [DOI] [PubMed] [Google Scholar]
  9. Cohen F. S., Akabas M. H., Zimmerberg J., Finkelstein A. Parameters affecting the fusion of unilamellar phospholipid vesicles with planar bilayer membranes. J Cell Biol. 1984 Mar;98(3):1054–1062. doi: 10.1083/jcb.98.3.1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Curran M. J., Cohen F. S., Chandler D. E., Munson P. J., Zimmerberg J. Exocytotic fusion pores exhibit semi-stable states. J Membr Biol. 1993 Apr;133(1):61–75. doi: 10.1007/BF00231878. [DOI] [PubMed] [Google Scholar]
  11. Dai J., Sheetz M. P. Mechanical properties of neuronal growth cone membranes studied by tether formation with laser optical tweezers. Biophys J. 1995 Mar;68(3):988–996. doi: 10.1016/S0006-3495(95)80274-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dai J., Sheetz M. P. Regulation of endocytosis, exocytosis, and shape by membrane tension. Cold Spring Harb Symp Quant Biol. 1995;60:567–571. doi: 10.1101/sqb.1995.060.01.060. [DOI] [PubMed] [Google Scholar]
  13. Helfrich W. Elastic properties of lipid bilayers: theory and possible experiments. Z Naturforsch C. 1973 Nov-Dec;28(11):693–703. doi: 10.1515/znc-1973-11-1209. [DOI] [PubMed] [Google Scholar]
  14. Hernandez L. D., Hoffman L. R., Wolfsberg T. G., White J. M. Virus-cell and cell-cell fusion. Annu Rev Cell Dev Biol. 1996;12:627–661. doi: 10.1146/annurev.cellbio.12.1.627. [DOI] [PubMed] [Google Scholar]
  15. Knoll G., Braun C., Plattner H. Quenched flow analysis of exocytosis in Paramecium cells: time course, changes in membrane structure, and calcium requirements revealed after rapid mixing and rapid freezing of intact cells. J Cell Biol. 1991 Jun;113(6):1295–1304. doi: 10.1083/jcb.113.6.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lindau M., Almers W. Structure and function of fusion pores in exocytosis and ectoplasmic membrane fusion. Curr Opin Cell Biol. 1995 Aug;7(4):509–517. doi: 10.1016/0955-0674(95)80007-7. [DOI] [PubMed] [Google Scholar]
  17. Markin V. S., Kozlov M. M., Borovjagin V. L. On the theory of membrane fusion. The stalk mechanism. Gen Physiol Biophys. 1984 Oct;3(5):361–377. [PubMed] [Google Scholar]
  18. Melikyan G. B., Niles W. D., Peeples M. E., Cohen F. S. Influenza hemagglutinin-mediated fusion pores connecting cells to planar membranes: flickering to final expansion. J Gen Physiol. 1993 Dec;102(6):1131–1149. doi: 10.1085/jgp.102.6.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Melikyan G. B., White J. M., Cohen F. S. GPI-anchored influenza hemagglutinin induces hemifusion to both red blood cell and planar bilayer membranes. J Cell Biol. 1995 Nov;131(3):679–691. doi: 10.1083/jcb.131.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Monck J. R., Alvarez de Toledo G., Fernandez J. M. Tension in secretory granule membranes causes extensive membrane transfer through the exocytotic fusion pore. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7804–7808. doi: 10.1073/pnas.87.20.7804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nagle J. F., Wilkinson D. A. Lecithin bilayers. Density measurement and molecular interactions. Biophys J. 1978 Aug;23(2):159–175. doi: 10.1016/S0006-3495(78)85441-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nanavati C., Markin V. S., Oberhauser A. F., Fernandez J. M. The exocytotic fusion pore modeled as a lipidic pore. Biophys J. 1992 Oct;63(4):1118–1132. doi: 10.1016/S0006-3495(92)81679-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Niles W. D., Silvius J. R., Cohen F. S. Resonance energy transfer imaging of phospholipid vesicle interaction with a planar phospholipid membrane: undulations and attachment sites in the region of calcium-mediated membrane--membrane adhesion. J Gen Physiol. 1996 Mar;107(3):329–351. doi: 10.1085/jgp.107.3.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oberhauser A. F., Fernandez J. M. Patch clamp studies of single intact secretory granules. Biophys J. 1993 Nov;65(5):1844–1852. doi: 10.1016/S0006-3495(93)81246-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ornberg R. L., Reese T. S. Beginning of exocytosis captured by rapid-freezing of Limulus amebocytes. J Cell Biol. 1981 Jul;90(1):40–54. doi: 10.1083/jcb.90.1.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Raphael R. M., Waugh R. E. Accelerated interleaflet transport of phosphatidylcholine molecules in membranes under deformation. Biophys J. 1996 Sep;71(3):1374–1388. doi: 10.1016/S0006-3495(96)79340-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Razinkov V. I., Melikyan G. B., Epand R. M., Epand R. F., Cohen F. S. Effects of spontaneous bilayer curvature on influenza virus-mediated fusion pores. J Gen Physiol. 1998 Oct;112(4):409–422. doi: 10.1085/jgp.112.4.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rubin R. J., Chen Y. D. Diffusion and redistribution of lipid-like molecules between membranes in virus-cell and cell-cell fusion systems. Biophys J. 1990 Nov;58(5):1157–1167. doi: 10.1016/S0006-3495(90)82457-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ryan T. A., Reuter H., Smith S. J. Optical detection of a quantal presynaptic membrane turnover. Nature. 1997 Jul 31;388(6641):478–482. doi: 10.1038/41335. [DOI] [PubMed] [Google Scholar]
  30. Sciaky N., Presley J., Smith C., Zaal K. J., Cole N., Moreira J. E., Terasaki M., Siggia E., Lippincott-Schwartz J. Golgi tubule traffic and the effects of brefeldin A visualized in living cells. J Cell Biol. 1997 Dec 1;139(5):1137–1155. doi: 10.1083/jcb.139.5.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Siegel D. P. Energetics of intermediates in membrane fusion: comparison of stalk and inverted micellar intermediate mechanisms. Biophys J. 1993 Nov;65(5):2124–2140. doi: 10.1016/S0006-3495(93)81256-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Solsona C., Innocenti B., Fernández J. M. Regulation of exocytotic fusion by cell inflation. Biophys J. 1998 Feb;74(2 Pt 1):1061–1073. doi: 10.1016/S0006-3495(98)74030-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Südhof T. C. The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature. 1995 Jun 22;375(6533):645–653. doi: 10.1038/375645a0. [DOI] [PubMed] [Google Scholar]
  34. Tse F. W., Iwata A., Almers W. Membrane flux through the pore formed by a fusogenic viral envelope protein during cell fusion. J Cell Biol. 1993 May;121(3):543–552. doi: 10.1083/jcb.121.3.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Waugh R. E. Surface viscosity measurements from large bilayer vesicle tether formation. II. Experiments. Biophys J. 1982 Apr;38(1):29–37. doi: 10.1016/S0006-3495(82)84527-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. White S. H. Studies of the physical chemistry of planar bilayer membranes using high-precision measurements of specific capacitance. Ann N Y Acad Sci. 1977 Dec 30;303:243–265. [PubMed] [Google Scholar]
  37. Zimmerberg J., Blumenthal R., Sarkar D. P., Curran M., Morris S. J. Restricted movement of lipid and aqueous dyes through pores formed by influenza hemagglutinin during cell fusion. J Cell Biol. 1994 Dec;127(6 Pt 2):1885–1894. doi: 10.1083/jcb.127.6.1885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zimmerberg J., Curran M., Cohen F. S. A lipid/protein complex hypothesis for exocytotic fusion pore formation. Ann N Y Acad Sci. 1991;635:307–317. doi: 10.1111/j.1749-6632.1991.tb36501.x. [DOI] [PubMed] [Google Scholar]

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