Journal of Bioenergetics and Biomembranes

, Volume 22, Issue 2, pp 157–179 | Cite as

Molecular mechanisms of calcium-induced membrane fusion

  • Demetrios Papahadjopoulos
  • Shlomo Nir
  • Nejat Düzgünes


We have reviewed studies on calcium-induced fusion of lipid bilayer membranes and the role of synexin and other calcium-binding proteins (annexins) in membrane fusion. We have also discussed the roles of other cations, lipid phase transitions, long chain fatty acids and other fusogenic molecules. Finally, we have presented a simple molecular model for the mechanism of lipid membrane fusion, consistent with the experimental evidence and incorporating various elements proposed previously.

Key Words

Liposomes annexins membrane-fusion model-membranes calcium lipid-bilayer calcium-binding-proteins 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahkong, Q. F., Fisher, D., Tampion, W., and Lucy, J. A. (1973). “The fusion of erythrocytes by fatty acids, esters, retinol and α-tocopherol,”Biochem. J. 136, 147–155.Google Scholar
  2. Akabas, M. H., Cohen, F. S., and Finkelstein, A. (1984). “Separation of the osmotically driven fusion event from vesicle-planar membrane attachment in a model system for exocytosis,”Cell Biol. 98, 1063.Google Scholar
  3. Allen, T. M., Hong, K., and Papahadjopoulos, D. (1990). “Membrane contact, fusion, and hexagonal (HII) transitions in phosphatidylethanolamine liposomes,”Biochemistry, in press.Google Scholar
  4. Baker, P. F. (1988). “Exocytosis in electropermeabilized cells: clues to mechanism and physiological control,” inMembrane Fusion in Fertilization, Cellular Transport, and Viral Infection (Düzgünes, N., and Bronner, F., eds), Academic Press, New York, pp. 115–138.Google Scholar
  5. Baker, P. F., and Knight, D. E. (1984). “Calcium control of exocytosis in bovine adrenal medullary cells,”Trends. Neurosci.,7, 120.Google Scholar
  6. Baker, P. F., Knight, D. E., and Whitaker, M. G. (1980). “Calcium and the control of exocytosis, inCalcium-Binding Proteins: Structure and Function” (Siegel, F. L., Carafoli, E., Kretsinger, R. H., MacLennan, D. H., and Wasserman, R. H., eds), Elsevier/North Holland, New York, pp. 47–55.Google Scholar
  7. Bangham, A. D., Standish, M. M., and Watkins, J. C. (1965). “Diffusion of univalent ions across lamellae of swollen phospholipids,”J. Mol. Biol. 13, 238.Google Scholar
  8. Bearer, E. L., Düzgünes, N., Friend, D. S., and Papahadjopoulos, D. (1982). “Fusion of phospholipid vesicles arrested by quick freezing. The question of lipidic particles as intermediates in membrane fusion,”Biochim. Biophys. Acta 693, 93.Google Scholar
  9. Bental, M., Wilschut, J., Scholma, J., and Nir, S. (1987). “Ca2+-induced fusion of large unilamellar phosphatidylserine/cholesterol vesicles,”Biochim. Biophys. Acta 898, 239.Google Scholar
  10. Bentz, J., and Düzgünes, N. (1985). “Fusogenic capacities of divalent cations and the effect of liposome size,”Biochemistry 24, 5436.Google Scholar
  11. Bentz, J., and Ellens, H. (1988). “Membrane fusion: kinetics and mechanisms,”Colloids Surf. 30, 65.Google Scholar
  12. Bentz, J., Nir, S., and Wilschut, J. (1983a). “Mass action kinetics of vesicle aggregation and fusion,”Colloids Surf. 6, 333.Google Scholar
  13. Bentz, J., Düzgünes, N., and Nir, S. (1983b). “Kinetics of divalent cation-induced fusion of phosphatidylserine vesicles: correlation between fusogenic capacities and binding affinities,”Biochemistry 22, 3320.Google Scholar
  14. Bentz, J., Düzgünes, N., and Nir, S. (1985). “Temperature dependence of divalent cation-induced fusion of phosphatidylserine liposomes: evaluation of the kinetic rate constants,”Biochemistry 24, 1064.Google Scholar
  15. Bentz, J., Alford, D., Cohen, J., and Düzgünes, N. (1988). “La3+-induced fusion of phosphatidylserine liposomes. Close approach, intermembrane intermediates, and the electrostatic membrane potential,”Biophys. J. 53, 593.Google Scholar
  16. Boni, L. T., Hah, J. S., Hui, S. W., Mukherjee, P., Ho, J. T., and Jung, C. Y. (1984).Biochim. Biophys. Acta 775, 409.Google Scholar
  17. Braun, G., Lelkes, P., and Nir, S. (1985). “Effect of cholesterol on Ca2+-induced aggregation and fusion of sonicated phosphatidylserine/cholesterol vesicles,”Biochim. Biophys. Acta 812, 688.Google Scholar
  18. Burns, A. L., Magendzo, K., Shirvan, A., Shrivastava, M., Rojas, E., Aligani, M. R., and Pollard, H. B. (1989). “Calcium channel activity of purified human synexin and structure of the human synexin gene.”Proc. Natl. Acad. Sci. USA 86, 3798.Google Scholar
  19. Chernomordik, L. V., Kozlov, M. M., Melikyan, G. B., Abidor, I. G., Markin, V. S., and Chizmadzhev, Y. A. (1985). “The shape of lipid molecules and monolayer membrane fusion,”Biochim. Biophys. Acta 812, 643.Google Scholar
  20. Chernomordik, L. V., Melikyan, G. B., and Chizmadzhev, Y. A. (1987). “Biomembrane fusion: a new concept derived from model studies using two interacting planar lipid bilayers,”Biochim. Biophys. Acta 906, 309.Google Scholar
  21. Creutz, C. E. (1981). “cis-Unsaturated fatty acids induce the fusion of chromaffin granules aggregated by synexin,”J. Cell Biol. 91, 247.Google Scholar
  22. Creutz, C. E., and Sterner, D. C. (1983). “Calcium dependence of the binding of synexin to isolated chromaffin granules,”Biochem. Biophys. Res. Commun. 114, 355.Google Scholar
  23. Creutz, C. E., Pazoles, C. J., and Pollard, H. B. (1978). Identification and purification of an adrenal medullary protein (synexin) that causes calcium-dependent aggregation of isolated chromaffin granules,”J. Biol. Chem. 253, 2858.Google Scholar
  24. Creutz, C. E., Pazoles, C. J., and Pollard, H. B. (1979). “Self-association of synexin in the presence of calcium: correlation with synexin-induced membrane fusion and examination of the structure of synexin aggregates,”J. Biol. Chem. 254, 553.Google Scholar
  25. Creutz, C. E., Dowling, L. G., Sando, J. J., Villar-Palasi, C., Whipple, J. H., and Zaks, W. J. (1983). “Characterization of the chromobindins: soluble proteins that bind to the chromaffin granule membrane in the presence of Ca2+,”J. Biol. Chem. 258, 14664.Google Scholar
  26. Creutz, C. E., Zaks, W. J., Hamman, H. C., and Martin, W. H. (1987). “The roles of Ca2+-dependent membrane-binding proteins in the regulation and mechanism of exocytosis, inCell Fusion (Sowers, A. E., ed.), Plenum Press, New York, pp. 45–68.Google Scholar
  27. Crompton, M. R., Moss, S. E., and Crumpton, M. J. (1988). “Diversity in the Lipocortin/calpactin family,”Cell 55, 1.Google Scholar
  28. Cullis, P. R., and Hope, M. J. (1978). “Effects of fusogenic agent on membrane structure of erythrocyte ghosts and the mechanism of membrane fusion,”Nature (London)271, 672.Google Scholar
  29. Cullis, P. R., and de Kruijff, B. (1979). “Lipid polymorphism and the functional roles of lipids in biological membranes,”Biochim. Biophys. Acta 559, 399.Google Scholar
  30. Cullis, P. R., and Verkleij, A. J. (1979). “Modulation of membrane structure by Ca2+ and dibucaine as detected by31P NMR,”Biochim. Biophys. Acta 552, 546.Google Scholar
  31. Dahl, G., Ekerdt, R., and Gratzl, M. (1979). “Models for exocytotic membrane fusion,”Symp. Soc. Exp. Biol. 33, 349.Google Scholar
  32. Das, S., and Rand, R. P. (1986). “Modification by diacylglycerol of the structure and interaction of various phospholipid bilayers,”Biochemistry,25, 2882.Google Scholar
  33. Dewald, B., Bretz, U., and Baggiolini, M. (1982). “Release of gelatinase from a novel secretory compartment of human neutrophils,”J. Clin. Invest. 70, 518.Google Scholar
  34. Drust, D. S., and Creutz, C. E. (1988). “Aggregation of chromaffin granules by calpactin at micromolar levels of calcium,”Nature (London)331, 88.Google Scholar
  35. Dunn, L. A., and Holz, R. W. (1983). “Catecholamine secretion from digitonin-treated adrenal medullary chromaffin cells,”J. Biol. Chem. 248, 4989.Google Scholar
  36. Düzgünes, N. (1985). “Membrane fusion,” inSubcellular Biochemistry, Vol. 11 (Roodyn, D. B., ed.), Plenum Press, New York, pp. 195–286.Google Scholar
  37. Düzgünes, N. (1988). “Cholesterol and membrane fusion,” inBiology of Cholesterol (Yeagle, P. L., ed.), CRC Press, Boca Raton, Florida, pp. 197–212.Google Scholar
  38. Düzgünes, N., and Papahadjopoulos, D. (1983). “Ionotropic effects on phospholipid membranes: calcium-magnesium specificity in binding, fluidity, and fusion,” inMembrane Fluidity in Biology, Vol. 2 (Aloia, R. C., ed.), Academic Press, New York, pp. 187–213.Google Scholar
  39. Düzgünes, N., and Hoekstra, D. (1986). “Agglutination and fusion of glycolipid-phospholipid vesicles mediated by lectins and calcium ions,”Stud. Biophys. 111, 5.Google Scholar
  40. Düzgünes, N., and Bentz, J. (1988). “Fluorescence assays for membrane fusion,” inSpectroscopic Membrane Probes,” Vol. 1 (Loew, L. M., ed.), CRC Press, Boca Raton, Florida, pp. 117–159.Google Scholar
  41. Düzgünes, N., Hong, K., and Papahadjopoulos, D. (1980). “Membrane fusion: the involvement of phospholipids, proteins, and calcium binding,” inCalcium-Binding Proteins: Structure and Function, (Siegel, F. L., Carafoli, E., Kretsinger, R. H., MacLennan, D. H. and Wasserman, R. H., eds), Elsevier/North-Holland, New York, pp. 17–22.Google Scholar
  42. Düzgünes, N., Nir, S., Wilschut, J., Bentz, J., Newton, C., Portis, A. and Papahadjopoulos, D. (1981a). “Calcium- and magnesium-induced fusion of mixed phosphatidylserine/phosphatidylcholine vesicles: effect of ion binding,”J. Membr. Biol. 59, 115.Google Scholar
  43. Düzgünes, N., Wilschut, J., Fraley, R., and Papahadjopoulos, D. (1981b). “Studies on the mechanism of membrane fusion: role of head-group composition in calcium- and magnesium-induced fusion of mixed phospholipid vesicles,”Biochim. Biophys. Acta 642, 182.Google Scholar
  44. Düzgünes, N., Paiement, J., Freeman, K. B., Lopez, N. G., Wilschut, J., and Papahadjopoulos, D. (1984a). “Modulation of membrane fusion by ionotropic and thermotropic phase transitions,”Biochemistry 23, 3486.Google Scholar
  45. Düzgünes, N., Hoekstra, D., Hong, K., and Papahadjopoulos, D. (1984b). “Lectins facilitate calcium-induced fusion of phospholipid vesicles containing glycosphingolipids,”FEBS Lett. 173, 80.Google Scholar
  46. Düzgünes, N., Wilschut, J., and Papahadjopoulos, D. (1985a). “Control of membrane fusion by divalent cations, phospholipid head-groups, and proteins, inPhysical Methods on Biological Membranes and their Model Systems (Conti, F., Blumberg, W. E., DeGier, J. and Pocchiari, F., eds), Plenum Press, New York, pp. 193–218.Google Scholar
  47. Düzgünes, N., Straubinger, R. M., Baldwin, P. A., Friend, D. S., and Papahadjopoulos, D. (1985b). “Proton-induced fusion of oleic acid-phosphatidylethanolamine liposomes,”Biochemistry 24, 3091.Google Scholar
  48. Düzgünes, N., Hong, K., Baldwin, P. A., Bentz, J., Nir, S., and Papahadjopoulos, D. (1987a). “Fusion of phospholipid vesicles induced by divalent cations and protons. Modulation by phase transitions, free fatty acids, monovalent cations, and polyamines,” inCell Fusion (Sowers, A. E., ed.), Plenum Press, New York, pp. 241–267.Google Scholar
  49. Düzgünes, N., Allen, T. M., Fedor, J., and Papahadjopoulos, D. (1987b). “Lipid mixing during membrane aggregation and fusion. Why fusion assays disagree,”Biochemistry 26, 8435.Google Scholar
  50. Düzgünes, N., Allen, T. M., Fedor, J., and Papahadjopoulos, D. (1988). “Why fusion assays disagree,” inMolecular Mechanisms of Membrane Fusion (Ohki, S., Doyle, D., Flanagan, T., Hui, S. W., and Mayhew, E., eds), Plenum Press, New York, pp. 543–555.Google Scholar
  51. Ekerdt, R., and Papahadjopoulos, D. (1982). “Intermembrane contact effects calcium binding to phospholipid vesicles,”Proc. Natl. Acad. Sci. USA 79, 2273.Google Scholar
  52. Ekerdt, R., Dahl, G., and Gratzl, M. (1981). “Membrane fusion of secretory vesicles and liposomes. Two different types of fusion,”Biochim. Biophys. Acta 646, 10.Google Scholar
  53. Ellens, H., Bentz, J., and Szoka, F. C. (1985). “H+-and Ca2+-induced fusion and destabilization of liposomes,”Biochemistry 24, 3099.Google Scholar
  54. Ellens, H., Bentz, J., and Szoka, F. C. (1986a). “Destabilization of phosphatidylethanolamine liposomes at the hexagonal phase transition temperature,”Biochemistry 25, 285.Google Scholar
  55. Ellens, H., Bentz, J., and Szoka, F. C. (1986b). “Fusion of phosphatidylethanolamine-containing liposomes and the mechanism of the Lα-HII phase transition,”Biochemistry 25, 4141.Google Scholar
  56. Ellens, H., Siegel, D. P., Alford, D., Yeagle, P. L., Boni, L., Lis, L. J., Quinn, P. J., and Bentz, J. (1989). “Membrane fusion and inverted phases,”Biochemistry 28, 3692.Google Scholar
  57. Ernst, J. D., Meers, P., Hong, K., Düzgünes, N., Papahadjopoulos, D., and Goldstein, I. M. (1986). “Human polymorphonuclear leukocytes contain synexin, a calcium-binding protein that mediates membrane fusion,”Trans. Assoc. Am. Physicians 49, 58.Google Scholar
  58. Feigenson, G. W. (1986). “On the nature of calcium ion binding between phosphatidylserine lamellae,”Biochemistry 25, 5819.Google Scholar
  59. Fraley, R., Wilschut, J., Düzgünes, N., Smith, C., and Papahadjopoulos, D. (1980). “Studies on the mechanism of membrane fusion: the role of phosphate in promoting calcium-induced fusion of phospholipid vesicles,”Biochemistry 19, 6021.Google Scholar
  60. Geisow, M. J. (1986). “Common domain structure of Ca2+ and lipid-binding proteinsFEBS Lett. 203, 99.Google Scholar
  61. Geisow, M. J., Walker, J. H., Boustead, C., and Taylor, W. (1987).Biosci. Rep. 7, 289.Google Scholar
  62. Gratzl, M., Schudt, C., Ekerdt, R., and Dahl, G. (1980). “Fusion of isolated biological membranes: a tool to investigate basic processes of exocytosis and cell-cell fusion,” inMembrane Structure and Function, Vol. 3 (Bittar, E. E., ed.), Wiley, New York, pp. 59–92.Google Scholar
  63. Gruner, S. M., Cullis, P. R., Hope, M. J., and Tilcock, C. P. S. (1985). “Lipid polymorphism. The molecular basis of nonbilayer phases,”Annu. Rev. Biophys. Biophys. Chem. 14, 211.Google Scholar
  64. Gruner, S. M., Tate, M. W., Kirk, G. L., So, P. T. C., Turner, D. C., Keane, D. T., Tilcock, C. P. S., and Cullis, P. R. (1988). “X-ray diffraction study of the polymorphic behavior of N-methylated dioleylphosphatidy ethanolamine,”Biochemistry 27, 2853.Google Scholar
  65. Hauser, H., Pascher, I., Pearson, R. H., and Sundell, S. (1981). “Preferred conformation and molecular packing of phosphatidylethanolamine and phosphatidylcholine,”Biochim. Biophys. Acta 650, 21.Google Scholar
  66. Helm, C. A., Israelachvilli, J. N., and McGuiggan, P. M. (1989). “Molecular mechanisms and forces involved in adhesion and fusion of bilayers,”Science 246, 919.Google Scholar
  67. Hoekstra, D. and Düzgünes, N. (1986). “Ricinus communis agglutinin-mediated agglutination and fusion of glycolipid-containing phospholipid vesicles. Effect of carbohydrate head-group size, calcium ions, and spermine,”Biochemistry 25, 1321.Google Scholar
  68. Hoekstra, D., and Wilschut, J. (1989). “Membrane fusion of artificial and biological membranes: Role of local membrane dehydration,” inWater Transport in Biological Membranes, Vol. 1 (Benga, G., ed.) CRC Press, Boca Raton, FL, pp. 143–176.Google Scholar
  69. Hoekstra, D., de Boer, T., Klappe, K., and Wilschut, J. (1984). “Fluorescence method for measuring the kinetics of fusion between biological membranes,”Biochemistry 23, 5675.Google Scholar
  70. Hong, K., Düzgünes, N., and Papahadjopoulos, D. (1981). “Role of synexin in membrane fusion,”J. Biol. Chem. 256, 3651.Google Scholar
  71. Hong, K., Düzgünes, N., and Papahadjopoulos, D. (1982a). “Modulation of membrane fusion by calcium-binding proteins,”Biophys. J. 37, 296.Google Scholar
  72. Hong, K., Düzgünes, N., Ekerdt, R., and Papahadjopoulos, D. (1982b). “Synexin facilitates fusion of specific phospholipid vesicles at divalent cation concentrations found intracellularly,”Proc. Natl. Acad. Sci. USA 70, 4942.Google Scholar
  73. Hong, K., Schuber, F., and Papahadjopoulos, D. (1983). “Polyamines. Biological modulators of membrane fusion,”Biochim. Biophys. Acta 732, 469.Google Scholar
  74. Hong, K., Düzgünes, N., Meers, P. R., and Papahadjopoulos, D. (1987). “Protein modulation of liposome fusion,” inCell Fusion (Sowers, A. E., ed.), Plenum Press, New York, pp. 269–284.Google Scholar
  75. Hope, M. J., Walker, D. C., and Cullis, P. R. (1983). “Calcium and pH-induced fusion of small unilamellar vesicles consisting of phosphatidylethanolamine and negatively charged phospholipids: a freeze-fracture study,”Biochem. Biophys. Res. Commun. 110, 15.Google Scholar
  76. Horn, R. G. (1984). “Direct measurement of the forces between two lipid bilayers and observation of their fusion,”Biochim. Biophys. Acta 778, 224.Google Scholar
  77. Hui, S. W., Stewart, T. P., Boni, L. T., and Yeagle, P. L. (1981). “Membrane fusion through point defects in bilayers,”Science 212, 921.Google Scholar
  78. Hui, S. S., Nir, S., Stewart, T. P., Boni, L. T., and Huang, S. K. (1988). “Kinetic measurements of fusion of phosphatidylserine-containing vesicles by electron microscopy and fluorometry,”Biochim. Biophys. Acta 941, 130.Google Scholar
  79. Jendrasiak, G. L., and Hasty, J. H. (1974). “The hydration of phospholipids,”Biochim. Biophys. Acta 337, 79–91.Google Scholar
  80. Kachar, B., Fuller, N., and Rand, P. R. (1986). “Morphological responses to calcium-induced interaction of phosphatidylserine-containing vesicles,”Biophys. J. 50, 779.Google Scholar
  81. Klee, C. B. (1988). “Ca2+-Dependent phospholipid- (and membrane-) binding proteins,”Biochemistry 27, 6645.Google Scholar
  82. Leikin, S. L., Kozlov, M. M., Chernomordik, L. V., Markin, V. S., and Chizmadzhev, Y. A. (1987). “Membrane fusion: overcoming the hydration barrier and local restructuring,”J. Theor. Biol. 129, 411.Google Scholar
  83. Luzzati, V., and Tardieu, A. (1974). “Lipid phases: structure and structural transitions,”Annu. Rev. Phys. Chem. 25, 79.Google Scholar
  84. MacDonald, R. I. (1985). “Membrane fusion due to dehydration by polyethylene glycol, dextran, or sucrose,”Biochemistry 24, 4058–4066.Google Scholar
  85. MacDonald, R. I., and MacDonald, R. C. (1983). “Lipid mixing during freeze-thawing of liposome membranes as monitored by fluorescence energy transfer,”Biochim. Biophys. Acta 735, 243.Google Scholar
  86. Markin, V. S., Kozlov, M. M., and Borovjagin, V. L. (1984). “On the theory of membrane fusion. The stalk mechanism,”Gen. Physiol. Biophys. 5, 361.Google Scholar
  87. Marra, J., and Israelachvili, J. (1985). “Direct measurements of forces between phosphatidylcholine and phosphatidylethanolamine bilayers in aqueous electrolyte solutions,”Biochemistry 24, 4608.Google Scholar
  88. McIntosh, T. J., Magid, A. D. and Simon, S. A. (1987). “Steric repulsion between phosphatidylcholine bilayers,”Biochemistry 26, 7325.Google Scholar
  89. Meers, P., Hong, K., Bentz, J., and Papahadjopoulos, D. (1986). “Spermine as a modulator of membrane fusion: interactions with acidic phospholipids,”Biochemistry 25, 3109.Google Scholar
  90. Meers, P., Ernst, J. D., Düzgünes, N., Hong, K., Fedor, J., Goldstein, I. M., and Papahadjopoulos, D. (1987a). “Synexin-like proteins from human polymorphonuclear leukocytes. Identification and characterization of granule-aggregating and membrane-fusing activities,”J. Biol. Chem. 262, 7850.Google Scholar
  91. Meers, P., Hong K., and Papahadjopoulos, D. (1987b). “Studies on the binding of synexin to phospholipid vesicles,” inProceedings of the Fifth International Symposium on Calcium Binding Proteins in Health and Disease (Norman, A. W., Vanaman, T. C., and Means, A. R., eds), Academic Press, Orlando, Florida, pp. 338–390.Google Scholar
  92. Meers, P., Bentz, J., Alford, D., Nir, S., Papahadjopoulos, D., and Hong, K. (1988a). “Synexin enhances the aggregation rate but not the fusion rate of liposomes,”Biochemistry 27, 4430.Google Scholar
  93. Meers, P., Hong, K., and Papahadjopoulos, D. (1988b). “Free fatty acid enhancement of cation-induced fusion of liposomes: synergism with synexin and other promoters of vesicle aggregation,”Biochemistry 27, 6784.Google Scholar
  94. Michell, R. H. (1975). “Inositol phospholipids and cell surface receptor function,”Biochim. Biophys. Acta 415, 81.Google Scholar
  95. Michell, R. H., Kirk, C. J., Jones, L. M., Downes, C. P., and Creba, J. A. (1981). “The stimulation action of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: defined characteristics and unanswered questions,”Philos. Trans. R. Soc. London B. 296, 123.Google Scholar
  96. Miller, D. C., and Dahl, G. P. (1982). “Early events in calcium-induced liposome fusion,”Biochim. Biophys. Acta 689, 165.Google Scholar
  97. Morris, S. J., Hughes, J. M. X., and Whittaker, V. P. (1982). “Purification and mode of action of synexin: a protein enhancing calcium-induced membrane aggregation,”J. Neurochem. 39, 529.Google Scholar
  98. Nir, S. (1984). “A model for cation adsorption in closed systems: application to calcium binding to phospholipid vesicles,”J. Colloid Interface Sci. 102, 313.Google Scholar
  99. Nir, S., Bentz, J., and Portis, A. R., Jr. (1980a). “Effect of cation concentrations and temperature on the rates of aggregation of acidic phospholipid vesicles. Application to fusion,”Adv. Chem. Ser. 188, 75.Google Scholar
  100. Nir, S., Bentz, J., and Wilschut, J. (1980b). “Mass action kinetics of phosphatidylserine vesicle fusion as monitored by coalescence of internal vesicle volumes,”Biochemistry 19, 6030.Google Scholar
  101. Nir, S., Bentz, J., and Düzgünes, N. (1981). “Two modes of reversible vesicle aggregation: particle size and the DLVO theory,”J. Colloid Interface Sci. 84, 266.Google Scholar
  102. Nir, S., Wilschut, J., and Bentz, J. (1982). “The rate of fusion of phospholipid vesicles and the role of bilayer curvature.Biochim. Biophys. Acta 688, 275.Google Scholar
  103. Nir, S., Bentz, J., Wilschut, J., and Düzgünes, N. (1983a). “Aggregation and fusion of phospholipid vesicles,”Prog. Surf. Sci. 13, 1.Google Scholar
  104. Nir, S., Düzgünes, N., and Bentz, J. (1983b). “Binding of monovalent cations to phosphatidylserine and modulation of Ca2+-and Mg2+-induced vesicle fusion,”Biochim. Biophys. Acta 735, 160.Google Scholar
  105. Nir, S., Stutzin, A., and Pollard, H. B. (1987). “Effect of synexin on aggregation and fusion of chromaffin granule ghosts at pH 6,”Biochim. Biophys. Acta 903, 309.Google Scholar
  106. Ohki, S. (1982). “A mechanism of divalent ion-induced phosphatidylserine membrane fusion,”Biochim. Biophys. Acta 689, 1.Google Scholar
  107. Ohki, S. (1984). “Effects of divalent cations, temperature, osmotic pressure gradient, and vesicle curvature on phosphatidylserine vesicle fusion,”J. Membr. Biol. 77, 265.Google Scholar
  108. Ohki, S., and Düzgünes, N. (1979). “Divalent cation-induced interaction of phospholipid vesicle and monolayer membranes,”Biochim. Biophys. Acta 552, 438.Google Scholar
  109. Ohki, S., and Ohshima, H. (1984). “Divalent cation-induced surface tension increase in acidic phospholipid membranes. Ion binding and membrane fusion,”Biochim. Biophys. Acta 776, 177.Google Scholar
  110. Ohki, S., Düzgünes, N., and Leonards, K. (1982). “Phospholipid vesicle aggregation: Effect of monovalent and divalent ions,”Biochemistry,21, 2127.Google Scholar
  111. Ohnishi, S.-I. (1988). “Fusion of viral envelopes with cellular membranes,” inMembrane Fusion in Fertilization, Cellular Transport, and Viral Infection (Düzgünes, N., and Bronner, F., eds.), Academic Press, New York, pp. 257–296.Google Scholar
  112. Papahadjopoulos, D., and Bangham, A. D. (1966). “Biophysical properties of phospholipids. II. Permeability of phosphatidylserine liquid crystals to univalent ions,”Biochim. Biophys. Acta 126, 185.Google Scholar
  113. Papahadjopoulos, D., Poste, G., Schaeffer, B. E., and Vail, W. J. (1974). “Membrane fusion and molecular segregation in phospholipid vesicles.”Biochim. Biophys. Acta 352, 10.Google Scholar
  114. Papahadjopoulos, D., Vail, W. J., Pangborn, W. A., and Poste, G. (1976). “Studies on membrane fusion. II. Induction of fusion in pure phospholipid membranes by calcium and other divalent metals,”Biochim. Biophys. Acta 448, 265.Google Scholar
  115. Papahadjopoulos, D., Vail, W. J., Newton, C., Nir, S., Jacobson, K., Poste, G., and Lazo, R. (1977). “Studies on membrane fusion. III. The role of calcium-induced phase changes,”Biochim. Biophys. Acta 465, 579.Google Scholar
  116. Papahadjopoulos, D., Poste, G., and Vail, W. J. (1979). “Studies on membrane fusion with natural and model membranes,”Methods Membr. Biol. 10, 1.Google Scholar
  117. Papahadjopoulos, D., Meers, P. R., Hong, K., Ernst, J. D., Goldstein, I. M., and Düzgünes, N. (1988). “Calcium-induced membrane fusion: from liposomes to cellular membranes,” inMolecular Mechanisms of Membrane Fusion (Ohki, S., Doyle, D., Flanagan, T., Hui, S. W., and Mayhew, E., eds), Plenum Press, New York, pp. 1–16.Google Scholar
  118. Parente, R. A., and Lentz, B. (1986). “Rate and extent of PEG-induced large vesicle fusion, monitored by bilayer and internal contents mixing,”Biochemistry 25, 6678.Google Scholar
  119. Pohl, H. A. (1978).Dielectrophoresis, Cambridge University Press, Cambridge.Google Scholar
  120. Pollard, H. B., and Scott, J. H. (1982). “Synhibin: a new calcium-dependent membrane-binding protein that inhibits synexin-induced chromaffin granule aggregation and fusion,”FEBS Lett. 150, 201.Google Scholar
  121. Portis, A., Newton, C., Pangborn, W. and Papahadjopoulos, D. (1979). “Studies on the mechanism of membrane fusion: evidence for an intermembrane Ca2+-phospholipid complex, synergism with Mg2+ and inhibition by spectrin,”Biochemistry 18, 780.Google Scholar
  122. Prestegard, J. H., and O'Brien, M. P. (1987). Membrane and vesicle fusion,”Annu. Rev. Phys. Chem. 38, 383.Google Scholar
  123. Rand, R. P. (1981). “Interacting phospholipid bilayers: measured forces and induced structural changes,”Annu. Rev. Biophys. Bioeng. 10, 277.Google Scholar
  124. Rand, R. P., Kachar, B., and Reese, T. S. (1985). “Dynamic morphology of calcium-induced interactions between phosphatidylserine vesicles,”Biophys. J. 47, 483.Google Scholar
  125. Rehfeld, S. J., Düzgünes, N., Newton, C., Papahadjopoulos, D., and Eatough, D. J. (1981). “The exothermic reaction of calcium with unilamellar phosphatidylserine vesicles: titration microcalorimetry,”FEBS Lett. 123, 249.Google Scholar
  126. Rosenberg, J., Düzgünes, N., and Kayalar, C. (1983). “Comparison of two liposome fusion assays monitoring the intermixing of aqueous contents and of membrane components.”Biochim. Biophys. Acta 735, 173.Google Scholar
  127. Rupert, L. A. M., van Breemen, J. F. L., van Bruggen, E. F. J., Engberts, J. B. F. N. and Hoekstra, D. (1987). “Calcium-induced fusion of didodecylphosphate vesicles: the lamellar to hexagonal II (HH) phase transition,”J. Membr. Biol. 95, 255.Google Scholar
  128. Schuber, F., Hong, K., Düzgünes, N., and Papahadjopoulos, D. (1983). “Polyamines as modulators of membrane fusion: aggregation and fusion of liposomes,”Biochemistry 22, 6134.Google Scholar
  129. Shavnin, S. A., Pedroso de Lima, M. C., Fedor, J., Wood, P., Bentz, J., and Düzgünes, N. (1988). “Cholesterol affects divalent cation-induced fusion and isothermal phase transitions of phospholipid membranes,”Biochim. Biophys. Acta 946, 405.Google Scholar
  130. Siegel, D. P. (1984). “Inverted micellar structures in bilayer membranes: Formation rates and half-lives,”Biophys. J. 45, 399.Google Scholar
  131. Siegel, D. P., Ellens, H., and Bentz, J. (1988). “Membrane fusion via intermediates in Lx/HH phase transitions,” inMolecular Mechanisms of Membrane Fusion (Ohki, S., Doyle, D., Flanagan, T., Hui, S. W., and Mayhew, E., eds), Plenum Press, New York, pp. 53–71.Google Scholar
  132. Siegel, D. P., Banschbach, J., Alford, D., Ellens, H., Lis, L. J., Quinn, P. J., Yeagle, P. L., and Bentz, J. (1989). “Physiological levels of diacylglycerols in phospholipid membranes induce membrane fusion and stabilize inverted phases,”Biochemistry 28, 3703.Google Scholar
  133. Stenson, W. F., and Parker, C. W. (1979). “Metabolism of arachidonic acid in ionophorestimulated neutrophils,”J. Clin. Invest. 64, 1457.Google Scholar
  134. Stollery, J. G., and Vail, W. J. (1977). “Interaction of divalent cations or basic proteins with phosphatidylethanolamine vesicles,”Biochim. Biophys. Acta 471, 372.Google Scholar
  135. Struck, D. K., Hoekstra, D., and Pagano, R. E. (1981). “Use of resonance energy transfer to monitor membrane fusion,”Biochemistry 20, 4093.Google Scholar
  136. Südhof, T. C., Walker, J. H., and Obrocki, J. (1982). “Calelectrin self-aggregates and promotes membrane aggregation in the presence of calcium,”EMBO J. 1, 1167.Google Scholar
  137. Südhof, T. C., Ebbecke, M., Walker, J. H., Fritsche, U., and Boustead, C. (1984). “Isolation of mammalian calelectrins: a new class of ubiquitous Ca2+-regulated proteins,”Biochemistry 23, 1103.Google Scholar
  138. Südhof, T. C., Slaughter, C. A., Leznicki, I., Barjon, P., and Reynolds, G. A. (1988). “Human 67-kDa calelectrin contains a duplication of four repeats found in 35-kDa lipocortins,”Proc. Natl. Acad. Sci. USA 85, 664.Google Scholar
  139. Sundler, R. (1984). “Role of phospholipid head group structure and polarity in the control of membrane fusion,”Biomembranes 12, 563.Google Scholar
  140. Sundler, R., and Papahadjopoulos, D. (1981). “Control of membrane fusion by phospholipid head groups. I. Phosphatidate/phosphatidylinositol specificity,”Biochim. Biophys. Acta 649, 743.Google Scholar
  141. Sundler, R., and Wijkander, J. (1983). “Protein-mediated intermembrane contact specifically enhances Ca2+-induced fusion of phosphatidate-containing membranes,”Biochim. Biophys. Acta 730, 391.Google Scholar
  142. Sundler, R., Düzgünes, N., and Papahadjopoulos, D. (1981). “Control of membrane fusion by phospholipid head groups. II. The role of phosphatidylethanolamine in mixtures with phosphatidate and phosphatidylinositol,”Biochim. Biophys. Acta 649, 751.Google Scholar
  143. Uster, P. S. and Deamer, D. W. (1981). “Fusion competence of phosphatidylserine-containing liposomes quantitatively measured by a fluorescence resonance energy transfer assay,”Arch. Biochem. Biophys. 209, 385.Google Scholar
  144. Verkleij, A. J. (1984). “Lipidic intramembranous particles,”Biochim. Biophys. Acta 779, 43.Google Scholar
  145. Verkleij, A. J., Mombers, C., Gerritsen, W. J., Leunissen-Bijvelt, L., and Cullis, P. R. (1979). “Fusion of phospholipid vesicles in association with the appearance of lipidic particles as visualized by freeze-fracturing,”Biochim. Biophys. Acta 555, 358.Google Scholar
  146. Verkleij, A. J., van Echteld, C. J. A., Gerritsen, W. J., Cullis, P. R., and de Kruijff, B. (1980). “The lipidic particle as an intermediate structure in membrane fusion processes and bilayer to hexagonal HII transitions,”Biochim. Biophys. Acta 600, 620.Google Scholar
  147. Verkleij, A. J., Leunissen-Bijvelt, J., de Kruijff, B., Hope, M., and Cullis, P. R. (1984). “Non-bilayer structures in membrane fusion,” inCell Fusion, Ciba Foundation Symposium 103, Pitman Books, London, pp. 45–59.Google Scholar
  148. Waite, M., DeChatelet, L. R., King, L., and Shirley, P. S. (1979). “Phagocytosis-induced release of arachidonic acid from human neutrophils,”Biochem. Biophys. Res. Commun. 90, 984.Google Scholar
  149. Walsh, C. E., Waite, B. M., Thomas, M. J., and DeChatelet, L. R. (1981). Release and metabolism of arachidonic acid in human neutrophils,J. Biol. Chem. 256, 7228.Google Scholar
  150. Wilschut, J. (1988). “Membrane interactions and fusion,” inEnergetics of Secretion Responses, Vol. II (Akkerman, J. W. N., ed.), CRC Press, Boca Raton, Florida, pp. 63–80.Google Scholar
  151. Wilschut, J., and Hoekstra, D. (1984). “Membrane fusion: from liposomes to biological membranes,”Trends Biochem. Sci. 9, 479.Google Scholar
  152. Wilschut, J., Düzgünes, N., Fraley, R., and Papahadjopoulos, D. (1980). “Studies on the mechanism of membrane fusion: kinetics of Ca2+-induced fusion of phosphatidylserine vesicles followed by a new assay for mixing of aqueous vesicle contents,”Biochemistry 19, 6011.Google Scholar
  153. Wilschut, J., Düzgünes, N., and Papahadjopoulos, D. (1981). “Calcium/magnesium specificity in membrane fusion: kinetics of aggregation and fusion of phosphatidylserine vesicles and the role of bilayer curvature,”Biochemistry 20, 3126.Google Scholar
  154. Wilschut, J., Düzgünes, N., Hong, K., Hoekstra, D., and Papahadjopoulos, D. (1983). “Retention of aqueous contents during divalent cation-induced fusion of phospholipid vesicles,”Biochim. Biophys. Acta 734, 309.Google Scholar
  155. Wilschut, J., Nir, S., Scholma, J., and Hoekstra, D. (1985a). “Kinetics of Ca2+-induced fusion of cardiolipin-phosphatidylcholine vesicles: correlation between vesicle aggregation, bilayer destabilization, and fusion,”Biochemistry 24, 4630.Google Scholar
  156. Wilschut, J., Scholma, J., Bental, M., Hoekstra, D., and Nir, S. (1985b). “Ca2+-induced fusion of phosphatidylserine vesicles: mass action kinetic analysis of membrane lipid mixing and aqueous contents mixing,”Biochim. Biophys. Acta 821, 45.Google Scholar
  157. Wilschut, J., Düzgünes, N., Hoekstra, D., and Papahadjopoulos, D. (1985c). “Modulation of membrane fusion by membrane fluidity: temperature dependence of divalent cation-induced fusion of phosphatidylserine vesicles,”Biochemistry 24, 8.Google Scholar
  158. Wilson, S. P., and Kirshner, N. (1983). “Calcium-evoked secretion from digitonin-permeabilized adrenal medullary chromaffin cells,”J. Biol. Chem. 258, 4994.Google Scholar
  159. Zimmermann, U. (1982). “Electric field-mediated fusion and related electrical phenomena,”Biochim. Biophys. Acta 694, 227.Google Scholar

Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Demetrios Papahadjopoulos
    • 1
    • 2
  • Shlomo Nir
    • 4
  • Nejat Düzgünes
    • 1
    • 3
  1. 1.Cancer Research InstituteUniversity of CaliforniaSan Francisco
  2. 2.Department of PharmacologyUniversity of CaliforniaSan Francisco
  3. 3.Department of Pharmaceutical ChemistryUniversity of CaliforniaSan Francisco
  4. 4.The Seagram Center, Faculty of AgricultureHebrew University of JerusalemRehovotIsrael

Personalised recommendations