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. 2000 May;78(5):2241–2256. doi: 10.1016/S0006-3495(00)76771-3

Dynamics of fusion pores connecting membranes of different tensions.

Y A Chizmadzhev 1, P I Kuzmin 1, D A Kumenko 1, J Zimmerberg 1, F S Cohen 1
PMCID: PMC1300816  PMID: 10777723

Abstract

The energetics underlying the expansion of fusion pores connecting biological or lipid bilayer membranes is elucidated. The energetics necessary to deform membranes as the pore enlarges, in some combination with the action of the fusion proteins, must determine pore growth. The dynamics of pore growth is considered for the case of two homogeneous fusing membranes under different tensions. It is rigorously shown that pore growth can be quantitatively described by treating the pore as a quasiparticle that moves in a medium with a viscosity determined by that of the membranes. Motion is subject to tension, bending, and viscous forces. Pore dynamics and lipid flow through the pore were calculated using Lagrange's equations, with dissipation caused by intra- and intermonolayer friction. These calculations show that the energy barrier that restrains pore enlargement depends only on the sum of the tensions; a difference in tension between the fusing membranes is irrelevant. In contrast, lipid flux through the fusion pore depends on the tension difference but is independent of the sum. Thus pore growth is not affected by tension-driven lipid flux from one membrane to the other. The calculations of the present study explain how increases in tension through osmotic swelling of vesicles cause enlargement of pores between the vesicles and planar bilayer membranes. In a similar fashion, swelling of secretory granules after fusion in biological systems could promote pore enlargement during exocytosis. The calculations also show that pore expansion can be caused by pore lengthening; lengthening may be facilitated by fusion proteins.

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Selected References

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  1. Breckenridge L. J., Almers W. Final steps in exocytosis observed in a cell with giant secretory granules. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1945–1949. doi: 10.1073/pnas.84.7.1945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chandler D. E., Whitaker M., Zimmerberg J. High molecular weight polymers block cortical granule exocytosis in sea urchin eggs at the level of granule matrix disassembly. J Cell Biol. 1989 Sep;109(3):1269–1278. doi: 10.1083/jcb.109.3.1269. [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. 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]
  5. Chernomordik L., Chanturiya A., Green J., Zimmerberg J. The hemifusion intermediate and its conversion to complete fusion: regulation by membrane composition. Biophys J. 1995 Sep;69(3):922–929. doi: 10.1016/S0006-3495(95)79966-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chizmadzhev Y. A., Cohen F. S., Shcherbakov A., Zimmerberg J. Membrane mechanics can account for fusion pore dilation in stages. Biophys J. 1995 Dec;69(6):2489–2500. doi: 10.1016/S0006-3495(95)80119-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chizmadzhev Y. A., Kumenko D. A., Kuzmin P. I., Chernomordik L. V., Zimmerberg J., Cohen F. S. Lipid flow through fusion pores connecting membranes of different tensions. Biophys J. 1999 Jun;76(6):2951–2965. doi: 10.1016/S0006-3495(99)77450-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Cohen F. S., Niles W. D. Reconstituting channels into planar membranes: a conceptual framework and methods for fusing vesicles to planar bilayer phospholipid membranes. Methods Enzymol. 1993;220:50–68. doi: 10.1016/0076-6879(93)20073-c. [DOI] [PubMed] [Google Scholar]
  10. Cohen F. S., Zimmerberg J., Finkelstein A. Fusion of phospholipid vesicles with planar phospholipid bilayer membranes. II. Incorporation of a vesicular membrane marker into the planar membrane. J Gen Physiol. 1980 Mar;75(3):251–270. doi: 10.1085/jgp.75.3.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Curran M. J., Brodwick M. S. Ionic control of the size of the vesicle matrix of beige mouse mast cells. J Gen Physiol. 1991 Oct;98(4):771–790. doi: 10.1085/jgp.98.4.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. Hochmuth F. M., Shao J. Y., Dai J., Sheetz M. P. Deformation and flow of membrane into tethers extracted from neuronal growth cones. Biophys J. 1996 Jan;70(1):358–369. doi: 10.1016/S0006-3495(96)79577-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leikin S., Kozlov M. M., Fuller N. L., Rand R. P. Measured effects of diacylglycerol on structural and elastic properties of phospholipid membranes. Biophys J. 1996 Nov;71(5):2623–2632. doi: 10.1016/S0006-3495(96)79454-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Markosyan R. M., Melikyan G. B., Cohen F. S. Tension of membranes expressing the hemagglutinin of influenza virus inhibits fusion. Biophys J. 1999 Aug;77(2):943–952. doi: 10.1016/S0006-3495(99)76945-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Marszalek P. E., Farrell B., Verdugo P., Fernandez J. M. Kinetics of release of serotonin from isolated secretory granules. II. Ion exchange determines the diffusivity of serotonin. Biophys J. 1997 Sep;73(3):1169–1183. doi: 10.1016/S0006-3495(97)78149-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Melikyan G. B., Jin H., Lamb R. A., Cohen F. S. The role of the cytoplasmic tail region of influenza virus hemagglutinin in formation and growth of fusion pores. Virology. 1997 Aug 18;235(1):118–128. doi: 10.1006/viro.1997.8686. [DOI] [PubMed] [Google Scholar]
  22. Melikyan G. B., Niles W. D., Cohen F. S. The fusion kinetics of influenza hemagglutinin expressing cells to planar bilayer membranes is affected by HA density and host cell surface. J Gen Physiol. 1995 Nov;106(5):783–802. doi: 10.1085/jgp.106.5.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Monck J. R., Oberhauser A. F., Alvarez de Toledo G., Fernandez J. M. Is swelling of the secretory granule matrix the force that dilates the exocytotic fusion pore? Biophys J. 1991 Jan;59(1):39–47. doi: 10.1016/S0006-3495(91)82196-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Niles W. D., Cohen F. S. Video fluorescence microscopy studies of phospholipid vesicle fusion with a planar phospholipid membrane. Nature of membrane-membrane interactions and detection of release of contents. J Gen Physiol. 1987 Nov;90(5):703–735. doi: 10.1085/jgp.90.5.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Parpura V., Fernandez J. M. Atomic force microscopy study of the secretory granule lumen. Biophys J. 1996 Nov;71(5):2356–2366. doi: 10.1016/S0006-3495(96)79483-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. 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]
  32. 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]
  33. 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]
  34. Trombetta E. S., Helenius A. Lectins as chaperones in glycoprotein folding. Curr Opin Struct Biol. 1998 Oct;8(5):587–592. doi: 10.1016/s0959-440x(98)80148-6. [DOI] [PubMed] [Google Scholar]
  35. Waugh R. E., Bauserman R. G. Physical measurements of bilayer-skeletal separation forces. Ann Biomed Eng. 1995 May-Jun;23(3):308–321. doi: 10.1007/BF02584431. [DOI] [PubMed] [Google Scholar]
  36. Weissenhorn W., Dessen A., Calder L. J., Harrison S. C., Skehel J. J., Wiley D. C. Structural basis for membrane fusion by enveloped viruses. Mol Membr Biol. 1999 Jan-Mar;16(1):3–9. doi: 10.1080/096876899294706. [DOI] [PubMed] [Google Scholar]
  37. Zimmerberg J., Cohen F. S., Finkelstein A. Fusion of phospholipid vesicles with planar phospholipid bilayer membranes. I. Discharge of vesicular contents across the planar membrane. J Gen Physiol. 1980 Mar;75(3):241–250. doi: 10.1085/jgp.75.3.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zimmerberg J., Curran M., Cohen F. S., Brodwick M. Simultaneous electrical and optical measurements show that membrane fusion precedes secretory granule swelling during exocytosis of beige mouse mast cells. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1585–1589. doi: 10.1073/pnas.84.6.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]

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