Cell Fusion pp 241-267 | Cite as

Fusion of Phospholipid Vesicles Induced by Divalent Cations and Protons

Modulation by Phase Transitions, Free Fatty Acids, Monovalent Cations, and Polyamines
  • Nejat Düzgüneş
  • Keelung Hong
  • Patricia A. Baldwin
  • Joe Bentz
  • Shlomo Nir
  • Demetrios Papahadjopoulos


Studies on the fusion of phospholipid vesicles have provided considerable insight into the molecular mechanism of membrane fusion and the role of specific molecules in this process. This simple and well-defined system has also helped in the development of fusion assays and the biophysical analysis of the fusion process. Early studies on fusion have been reviewed by Papahadjopoulos et al(1979) and Nir et al(1983a). Here we will discuss recent developments concerning the mechanism of membrane fusion induced by divalent cations and protons, and its modulation by the thermotropic properties of the phospholipid bilayer, monovalent cations and polyamines in the medium, and free fatty acids in the membrane.


Divalent Cation Membrane Fusion Monovalent Cation Phospholipid Vesicle Lipidic Particle 
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.

Abbreviations used in this chapter


1, aminonapthalene-3,6,8-trisulfonic acids






dipicolinic acid












p-xylylene-bis-pyridinium bromide


large unilamellar vesicles (approx. 100-nm diameter)




phosphatidate (phosphatidic acid)


(egg) phosphatidylcholine


(egg) phosphatidylethanolamine






(bovine brain) phosphatidylserine


small unilamellar vesicles (approx. 30-nm diameter)


temperature range of the lamellar-hexagonal phase transition


phosphatidylethanolamine synthesized by transphosphatidylation of egg phosphatidylcholine.


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  1. Baldwin, P. A., Düzgüneş, N., and Papahadjopoulos, D., 1985, Free fatty acids affect H+and Ca2+-induced fusion of model membranes, Biophys. J.47:112a.Google Scholar
  2. Baldwin, P. A., Düzgüneş, N., and Papahadjopoulos, D., 1986, The fate of liposome contents during proton-induced fusion is affected by hexagonal phase transitions in liposomes composed of fatty acids and phosphatidylethanolamine, in preparation.Google Scholar
  3. Bangham, A. D., 1968, Membrane models with phospholipids, Prog. Biophys. Mol. Biol. 18:29–95.PubMedCrossRefGoogle Scholar
  4. Bangham, A. D., Standish, M. M., and Watkins, J. C., 1965, Diffusion of univalent ions across lamellae of swollen phospholipids, J. Mol. Biol. 13:238–252.PubMedCrossRefGoogle Scholar
  5. Bearer, E. L., Düzgüneş, 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 693:93–98.PubMedCrossRefGoogle Scholar
  6. Bentz, J., and Düzgüneş, N., 1985, Fusogenic capacities of divalent cations and effect of liposome size, Biochemistry 24:5436–5443.PubMedCrossRefGoogle Scholar
  7. Bentz, J., Nir, S., and Wilschut, J., 1983a, Mass action kinetics of vesicle aggregation and fusion, Colloids Surfaces 6:333–363.CrossRefGoogle Scholar
  8. Bentz, J., Düzgüneş, N., and Nir, S., 1983b, Kinetics of divalent cation induced fusion of phosphatidylserine vesicles: Correlation between fusogenic capacities and binding affinities, Biochemistry 22: 3320–3330.CrossRefGoogle Scholar
  9. Bentz, J., Düzgüneş, N., and Nir, S., 1985a, Temperature dependence of divalent cation induced fusion of phosphatidylserine liposomes: Evaluation of the kinetic rate constants, Biochemistry 24:1064–1072.PubMedCrossRefGoogle Scholar
  10. Bentz, J., Ellens, H., Lai, M. Z., and Szoka, F. C., Jr., 1985b, On the correlation between HIIphase and the contact-induced destabilization of phosphatidylethanolamine-contain-ing membranes, Proc. Natl Acad Sci. USA. 82:5742–5745.PubMedCrossRefGoogle Scholar
  11. Boggs, J. M., Moscarello, M. A., and Papahadjopoulos, D., 1982, Interactions of myelin proteins with phospholipid membranes, in: The Molecular Biology of Lipid-Protein Interactions, Vol. 2 (O. H. Griffith and P. Jost, eds.), pp. 1–51, Wiley, New York.Google Scholar
  12. Braun, G., Lelkes, P. I., and Nir, S., 1985, Effect of cholesterol on Ca2+-induced aggregation and fusion of sonicated phosphatidylserine/cholesterol vesicles, Biochim. Biophys. Acta 812:688–694.PubMedCrossRefGoogle Scholar
  13. Chernomordik, L. V., Kozlov, M. M., Melikyan, G. B., Abidor, I. G., Markin, V. S., and Chiz-madzhev, Y. A., 1985, The shape of lipid molecules and monolayer membrane fusion, Biochim. Biophys. Acta 812:643–655.CrossRefGoogle Scholar
  14. Cullis, P. R., and DeKruijff, B., 1979, Lipid polymorphism and the functional roles of lipids in biological membranes, Biochim. Biophys. Acta 559:399–420.PubMedCrossRefGoogle Scholar
  15. 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 (Lond.) 271:672–674.CrossRefGoogle Scholar
  16. Cullis, P. R., and Verkleij, A. J., 1979, Modulation of membrane structure by Ca2+and dibucaine as detected by 31P-NMR, Biochim. Biophys. Acta 552:546–551.PubMedCrossRefGoogle Scholar
  17. Day, E. P., Kwok, A. Y. W., Hark, S. K., Ho, J. T., Vail, W. J., Bentz, J., and Nir, S., 1980, Reversibility of sodium-induced aggregation of sonicated phosphatidylserine vesicles. Proc. Natl. Acad. Sci. USA. 77:4026–4029.PubMedCrossRefGoogle Scholar
  18. Düzgüneş, N., 1985, Membrane fusion. Subcell. Biochemistry 11:195–286.Google Scholar
  19. Düzgüneş, N., and Hoekstra, D., 1986, Agglutination and fusion of glycolipid-phospholipid vesicles mediated by lectins and calcium ions, Stud. Biophys. 111:5–10.Google Scholar
  20. Düzgüneş, N., and Papahadjopoulos, D., 1983, Ionotropic effects on phospholipid membranes: Calcium-magnesium specificity in binding, fluidity, and fusion, in: Membrane Fluidity in BiologyVol. 2: General Principles(R. C. Aloia, ed.), pp. 187–216, Academic Press, New York.Google Scholar
  21. Düzgüneş, N., Hong, K., and Papahadjopoulos, D., 1980, Membrane fusion: The involvement of phospholipids, proteins and calcium binding, in: Calcium-Binding Proteins: Structure and Function(F. L. Siegel, E. Carafoli, R. H. Kretsinger, D. H. MacLennan, and R. H. Wasserman, eds.), pp. 17–22, Elsevier/North-Holland, New York.Google Scholar
  22. Düzgüneş, N., Nir, S., Wilschut, J., Bentz, J., Newton, C., Portis, A., and Papahadjopoulos, D., 1981a, Calcium- and magnesium-induced fusion of mixed phosphatidylserine/phos-phatidylcholine vesicles: Effect of ion binding, J. Membrane Biol. 59:115–125.CrossRefGoogle Scholar
  23. Düzgüneş, N., Wilschut, J., Fraley, R., and Papahadjopoulos, D., 1981c, 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 642:182–195.PubMedCrossRefGoogle Scholar
  24. Düzgüneş, N., Straubinger, R. M., and Papahadjopoulos, D., 1983, pH-dependent membrane fusion,J. Cell Biol.97:178a.CrossRefGoogle Scholar
  25. Düzgüneş, 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 23:3486–3494.PubMedCrossRefGoogle Scholar
  26. Düzgüneş, N., Hoekstra, D., Hong, K., and Papahadjopoulos, D., 1984b, Lectins facilitate calcium-induced fusion of phospholipid vesicles containing glycosphingolipids, FEBS Lett. 173:80–84.PubMedCrossRefGoogle Scholar
  27. Düzgüneş, N., Wilschut, J., and Papahadjopoulos, D., 1985a, Control of membrane fusion by divalent cations, phospholipid head-groups and proteins, in: Physical Methods on Biological Membranes and Their Model Systems(F. Conti, W. E. Blumberg, J. DeGier, and F. Pocchiari, eds.), pp. 193–218, Plenum Press, New York.CrossRefGoogle Scholar
  28. Düzgüneş, N., Straubinger, R. M., Baldwin, P. A., Friend, D. S., and Papahadjopoulos, D., 1985c, Proton-induced fusion of oleic acid-phosphatidylethanolamine liposomes, Biochemistry 24:3091–3098.PubMedCrossRefGoogle Scholar
  29. Eisenberg, M., Gresalfi, T., Riccio, T., and McLaughlin, S., 1979, Adsorption of monovalent cations to bilayer membranes containing negative phospholipids, Biochemistry 18:5213–5223.PubMedCrossRefGoogle Scholar
  30. Ekerdt, R., and Papahadjopoulos, D., 1982, Intermembrane contact affects calcium binding to phospholipid vesicles, Proc. Natl. Acad. Sci. USA. 79:2273–2277.PubMedCrossRefGoogle Scholar
  31. Eliasz, A. W., Chapman, D., and Ewing, D. F., 1976, Phospholipid phase transitions. Effects of n-alcohols, n-monocarboxylic acids, phenylalkyl alcohols and quaternary ammonium compounds, Biochim. Biophys. Acta 448:220–230.PubMedCrossRefGoogle Scholar
  32. Ellens, H., Bentz, J., and Szoka, F. C., 1984, pH-induced destabilization of phosphati-dylethanolamine-containing liposomes. Role of bilayer contact, Biochemistry 23:1532–1538.PubMedCrossRefGoogle Scholar
  33. Ellens, H., Bentz, J., and Szoka, F. C., 1985, H+- and Ca2+-induced fusion and destabilization of liposomes, Biochemistry 24:3099–3106.PubMedCrossRefGoogle Scholar
  34. Ellens, H., Bentz, J., and Szoka, F. C., 1986a, Destabilization of phosphatidylethanolamine liposomes at the hexagonal phase transition temperature, Biochemistry 25:285–294.PubMedCrossRefGoogle Scholar
  35. Ellens, H., Bentz, J., and Szoka, F. C., 1986c, Fusion of phosphatidylethanolamine-contain-ing liposomes and the mechanism of the La-HIIphase transition, Biochemistry,25:4141–4147.PubMedCrossRefGoogle Scholar
  36. Findlay, E. J., and Barton, P. G., 1978, Phase behavior of synthetic phosphatidylglycerols and binary mixtures with phosphatidylcholines in the presence and absence of calcium ions, Biochemistry 17:2400–2405.PubMedCrossRefGoogle Scholar
  37. Gagné, J., Stamatatos, L., Diacovo, T., Hui, S. W., Yeagle, P., and Silvius, J., 1985, Physical properties and surface interactions of bilayer membranes containing N-methylated phosphatidylethanolamines, Biochemistry 24:4400–4408.PubMedCrossRefGoogle Scholar
  38. Galla, H. J., and Sackmann, E., 1975, Chemically induced lipid phase separation in model membranes containing charged lipids: A. spin label study, Biochim. Biophys. Acta 401:509–529.PubMedCrossRefGoogle Scholar
  39. Geuze, H. J., Slot, J. W., Strous, G. J. A. M., Lodish, H. F., and Schwartz, A. L., 1983, Intracellular site of asialoglycoprotein receptor-ligand uncoupling: Double label immunoelectrin microscopy during receptor-mediated endocytosis, Cell 32:277–287.PubMedCrossRefGoogle Scholar
  40. Graham, L, Gagné, J., and Silvius, J. R., (1985), Kinetics and thermodynamics of calcium-induced lateral phase separations in phosphatic acid containing bilayers, Biochemistry 24:7123–7131.PubMedCrossRefGoogle Scholar
  41. 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. 14:211–238.PubMedCrossRefGoogle Scholar
  42. Harlos, K., and Eibl H., 1980, Influence of calcium on phosphatidylethanolamine. An investigation of the structure at high pH, Biochim. Biophys. Acta 601:113–122.PubMedCrossRefGoogle Scholar
  43. Hauser, H., and Shipley, G. G., 1983, Interactions of monovalent cations with phosphatidyl-serine bilayer membranes, Biochemistry 22:2172–2178.Google Scholar
  44. Hauser, H., Pascher, I., Pearson, R. H., and Sundell, S., 1981, Preferred conformation and molecular packing of phosphatidylethanolamine and phosphatidylcholine, Biochim. Biophys. Acta 650:21–51.PubMedCrossRefGoogle Scholar
  45. Hoekstra, D., 1982a, Fluorescence method for measuring the kinetics of Ca2+-induced phase separations in phosphatidylserine-containing lipid vesicles, Biochemistry 21:1055–1061.PubMedCrossRefGoogle Scholar
  46. Hoekstra, D., 1982c, Role of lipid phase separations and membrane hydration in phospholipid vesicle fusion. Biochemistry 21:2833–2840.PubMedCrossRefGoogle Scholar
  47. Hoekstra, D., Düzgüneş, N., and Wilschut, J., 1985, Agglutination and fusion of globoside GL-4 containing phospholipid vesicles mediated by lectins and Ca2+, Biochemistry 24:565–572.PubMedCrossRefGoogle Scholar
  48. Hoekstra, D., and Düzgüneş, N., 1986, Ricinus communisagglutinin-mediated agglutination and fusion of glycolipid-containing phospholipid vesicles. Effect of carbohydrate head group size, calcium ions and spermine, Biochemistry 25:1321–1330.PubMedCrossRefGoogle Scholar
  49. Hong, K., Schuber, F., and Papahadjopoulos, D., 1983, Polyamines: Biological modulators of membrane fusion, Biochim. Biophys. Acta 732:469–472.PubMedCrossRefGoogle Scholar
  50. 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. 110:15–22.PubMedCrossRefGoogle Scholar
  51. Huang, C. C., 1969, Studies on phosphatidylcholine vesicles: Formation and physical characteristics, Biochemistry 8:344–352.PubMedCrossRefGoogle Scholar
  52. Hui, S. W., 1981, Geometry of phase separated domains in phospholipid bilayers by diffraction-contrast electron microscopy, Biophys. J. 34:383–395.PubMedCrossRefGoogle Scholar
  53. Hui, S. W., Stewart, T. P., Boni, L. T., and Yeagle, P. L., 1981, Membrane fusion through point defects in bilayers, Science 212:921–923.PubMedCrossRefGoogle Scholar
  54. Hui, S. W., Boni, L. T., Stewart, T. P., and Isaac, T., 1983, Identification of phosphatidylserine and phosphatidylcholine in calcium-induced phase separated domains, Biochemistry 22:3511–3516.CrossRefGoogle Scholar
  55. Ito, T., and Ohnishi, S. 1974, Ca2+-induced lateral phase separations in phosphatide acid- phosphatidylcholine membranes, Biochim. Biophys. Acta 352:29–37.PubMedCrossRefGoogle Scholar
  56. Jacobson, K., and Papahadjopoulos, D., 1975, Phase transitions and phase separations in phospholipid membranes induced by changes in temperature, pH and concentration of bivalent cations, Biochemistry 14:152–161.PubMedCrossRefGoogle Scholar
  57. Jendrasiak, G. L., and Hasty, J. H., 1974, The hydration of phospholipids, Biochim. Biophys. Acta 337:79–91.PubMedCrossRefGoogle Scholar
  58. Kolber, M. A., and Haynes, D. H., 1979, Evidence for A. role of phosphatidylethanolamine as a modulator of membrane-membrane contact,J. Membrane Biol. 48:95–114.CrossRefGoogle Scholar
  59. Kurland, R., Newton, C., Nir, S., and Papahadjopoulos, D., 1979, Specificity of Na+binding to phosphatidylserine vesicles from A. 23Na+NMR relaxation rate study, Biochim. Biophys. Acta 551:137–147.PubMedCrossRefGoogle Scholar
  60. Lai, M-Z., Vail, W. J., and Szoka, F. C., 1985, Acid- and calcium-induced structural changes in phosphatidylethanolamine membranes stabilized by cholesterol hemisuccinate, Biochemistry 24:1654–1661.PubMedCrossRefGoogle Scholar
  61. Lis, L. J., McAlister, M., Fuller, N., Rand, R. P., and Parsegian, V. A., 1982, Interactions between neutral phospholipid bilayer membranes, Biophys. J. 37:657–666.PubMedGoogle Scholar
  62. Loosley-Millman, M. E., Rand, R. P., and Parsegian, V. A., 1982, Effects of monovalent ion binding and screening on measured electrostatic forces between charged phospholipid bilayers, Biophys. J. 40:221–232.PubMedCrossRefGoogle Scholar
  63. Markin, V. S., Kozlov, M. M., and Borovjagin, V. L., 1984, On the theory of membrane fusion. The stalk mechanism, Gen. Physiol. Biophys. 5:361–377.Google Scholar
  64. Marsh, M., 1984, The entry of enveloped viruses into cells by endocytosis, Biochem. J.218:1–10.PubMedGoogle Scholar
  65. Mayer, L. D., and Nelsestuen, G. L., 1981, Calcium- and prothrombin-induced lateral phase separation in membranes, Biochemistry 20:2457–2463.PubMedCrossRefGoogle Scholar
  66. McLaughlin, S. G. A., Szabo, G., and Eisenman, G., Divalent ions and the surface potential of charged phospholipid membranes,J. Gen. Physiol. 58:667–687.Google Scholar
  67. Mclver, D. J. L., 1970, Control of membrane fusion by interfacial water: A. model for the action of divalent cations, Physiol Chem. Phys. 11:289–302.Google Scholar
  68. McLaughlin, S., Mulrine, N., Gresalfi, T., Vaio, G., and McLaughlin, A., 1981, The adsorption of divalent cations to bilayer membranes containing phosphatidylserine, J. Gen. Physiol 77:445–473.PubMedCrossRefGoogle Scholar
  69. Meers, P., Hong, K., Bentz, J., and Papahadjopoulos, D., 1986, Spermine as A. modulator of membrane fusion: Interaction with acidic phospholipids, Biochemistry 25:3109–3118.PubMedCrossRefGoogle Scholar
  70. Michell, R. H., 1975, Inositol phospholipids and cell surface receptor function, Biochim. Biophys.Acta 415:81–147.PubMedCrossRefGoogle Scholar
  71. Michell, R. H., Kirk, C. J., Jones, L. M., Downes, C. P., and Creba, J. A., 1981, The stimulation of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: Defined characteristics and unanswered questions, Philos. Trans. R. Soc. Lond. B. 296:123–137.CrossRefGoogle Scholar
  72. Miller, D. C., and Dahl, G. P., 1982, Early events in calcium-induced liposome fusion, Biochim. Biophys. Acta 689:165–169.PubMedCrossRefGoogle Scholar
  73. Newton, C., Pangborn, W., Nir, S., and Papahadjopoulos, D., 1978, Specificity of Ca2+and Mg2+binding to phosphatidylserine vesicles and resultant phase changes of bilayer membrane structure, Biochim. Biophys. Acta 506:281–287.PubMedCrossRefGoogle Scholar
  74. Nir, S., 1984, A. model for cation adsorption in closed systems: Application to calcium binding to phospholipid vesicles,J. Colloid Interface Sci. 102:313–321.CrossRefGoogle Scholar
  75. Nir, S., and Bentz, J., 1978, On the forces between phospholipid bilayers,J. Colloid Interface Sci. 65:399–414.CrossRefGoogle Scholar
  76. Nir, S., Newton, C., and Papahadjopoulos, D., 1978, Binding of cations to phosphatidylserine vesicles, Bioelectrochem. Bioenerg. 5:116–133.CrossRefGoogle Scholar
  77. Nir, S., Bentz, J., and Wilschut, J., 1980a, Mass action kinetics of phosphatidylserine vesicle fusion as monitored by coalescence of internal vesicle volumes, Biochemistry 19:6030–6036.PubMedCrossRefGoogle Scholar
  78. Nir, S., Bentz, J., and Portis, A. R. Jr., 1980b, Effect of cation concentrations and temperature on the rates of aggregation of acidic phospholipid vesicles. Application to fusion, Adv. Chem. Ser. 188:75–106.CrossRefGoogle Scholar
  79. Nir, S., Bentz, J., and Düzgüneş, N., 1981, Two modes of reversible vesicle aggregation: Particle size and the DLVO theory, J. Colloid Interface Sci. 84:266–269.CrossRefGoogle Scholar
  80. Nir, S., Wilschut, J., and Bentz, J., 1982, The rate of fusion of phospholipid vesicles and the role of bilayer curvature, Biochim. Biophys. Acta 688:275–278.PubMedCrossRefGoogle Scholar
  81. Nir, S., Bentz, J., Wilschut, J., and Düzgüneş, N., 1983a, Aggregation and fusion of phospholipid vesicles, Prog. Surface Sci. 13:1–124.CrossRefGoogle Scholar
  82. Nir, S., Düzgüneş, N., and Bentz, J., 1983b, Binding of monovalent cations to phosphatidyl-serine and modulation of Ca2+- and Mg2+-induced vesicle fusion, Biochim. Biophys. Acta 735:160–172.PubMedCrossRefGoogle Scholar
  83. Ohki, S., 1982, A. mechanism of divalent-ion induced phosphatidylserine membrane fusion, Biochim. Biophys. Acta 689:1–11.PubMedCrossRefGoogle Scholar
  84. Ohki, S., and Düzgüneş, N., 1979, Divalent cation induced interaction of phospholipid vesicle and monolayer membranes, Biochim. Biophys. Acta 552:438–449.PubMedCrossRefGoogle Scholar
  85. Ohki, S., Düzgüneş, N., and Leonards, K., 1982, Phospholipid vesicle aggregation: Effect of monovalent and divalent ions, Biochemistry 21:2127–2133.PubMedCrossRefGoogle Scholar
  86. Ohki, S., Roy, S., Ohshima, H., and Leonards, K., 1984, Monovalent cation-induced phospholipid vesicle aggregation: Effect of ion binding, Biochemistry 23:6126–6132.PubMedCrossRefGoogle Scholar
  87. Ohnishi, S. I. and Ito, T., 1974, Calcium-induced phase separations in phosphatidylserine-phosphatidylcholine membranes, Biochemistry 13:881–887.CrossRefGoogle Scholar
  88. Ohnishi, S. I., and Tokutomi, S., 1981, ESR studies of calcium- and proton-induced phase separations in phosphatidylserine-phosphatidylcholine mixed membranes, in: Biological Magnetic Resonance, Vol. 3 (L. J. Berliner and J. Reuben, eds.), pp. 121–153, Plenum Press, New York.Google Scholar
  89. Ornberg, R. L., and Reese, T. S., 1981, Beginning of exocytosis captured by rapid-freezing of Limulusamebocytes, J. Cell Biol. 90:40–54.PubMedCrossRefGoogle Scholar
  90. Papahadjopoulos, D., 1968, Surface properties of acidic phospholipids: Interaction of monolayers and hydrated liquid crystals with uni- and bivalent metal ions, Biochim. Biophys. Acta 163:240–254.PubMedCrossRefGoogle Scholar
  91. Papahadjopoulos, D., 1973, Phospholipid membranes as experimental models for biological membranes, in: Biological Horizons in Surface Science(L. M. Prince and D. F. Sears, eds.), pp. 159–225, Academic Press, New York.Google Scholar
  92. Papahadjopoulos, D., 1978, Calcium-induced phase changes and fusion in natural and model membranes, in: Membrane Fusion(G. Poste and G. L. Nicolson, eds.), pp. 765–790, Elsevier/North-Holland, Amsterdam.Google Scholar
  93. Papahadjopoulos, D., and Watkins, J. C., 1967, phospholipid model membranes. II. Permeability properties of hydrated liquid crystals, Biochim. Biophys. Acta 135:630–652.Google Scholar
  94. Papahadjopoulos, D., Poste, G., Schaeffer, B. E., and Vail, W. J., 1974, Membrane fusion and molecular segregation in phospholipid vesicles, Biochim. Biophys. Acta 352:10–28.PubMedCrossRefGoogle Scholar
  95. 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 448:265–283.PubMedCrossRefGoogle Scholar
  96. 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 465:579–598.PubMedCrossRefGoogle Scholar
  97. Papahadjopoulos, D., Portis, A., and Pangborn, W., 1978a, Calcium-induced lipid phase transitions and membrane fusion. Ann. N.Y. Acad. Sci. 308:50–66.PubMedCrossRefGoogle Scholar
  98. Papahadjopoulos, D., Portis, A., Pangborn, W., and Newton, C., 1978b, Fusion of artificial membranes with special emphasis on the role of calcium-induced lipid phase transitions, in: Transport of Macromolecules in Cellular Systems(S. C. Silverstein, ed.), pp. 413–430, Dahlem Konferenzen, Berlin.Google Scholar
  99. Papahadjopoulos, D., Poste, G., and Vail, W. J., 1979, Studies on membrane fusion with natural and model membranes, Methods Membrane Biol. 10:1–121.CrossRefGoogle Scholar
  100. Portis, A., Newton, C., Pangborn, W., and Papahadjopoulos, D., 1979, Studies on the mechanism of membrane fusion: Evidence for an intermembrane Ca2+-phospho-lipid complex, synergism with Mg2+, and inhibition by spectrin, Biochemistry 18: 780–790.PubMedCrossRefGoogle Scholar
  101. Puskin, J., 1977, Divalent cation binding to phospholipids: An EPR study, J. Membrane Biol. 35:39–55.CrossRefGoogle Scholar
  102. Recktenwald, D. J., and McConnell, H., 1981, Phase equilibria in binary mixtures of phosphatidylcholine and cholesterol, Biochemistry 20:4505–4510.PubMedCrossRefGoogle Scholar
  103. Rehfeld, S. J., Düzgüneş, N., Newton, C., Papahadjopoulos, D., and Eatough, D. J., The exothermic reaction of calcium with unilamellar phosphatidylserine vesicles: Titration microcalorimetry, FEBS Lett. 123:249–251.Google Scholar
  104. Rosenberg, J., Düzgüneş, N., and Kayalar, C., 1983, Comparison of two liposome fusion assays monitoring the intermixing of aqueous contents and of membrane components, Biochim. Biophys. Acta 735:173–180.PubMedCrossRefGoogle Scholar
  105. Scherphof, G. L., 1983, A. matter of pronunciation, in: Liposome Letters(A. D. Bangham, ed.), pp. 319–321, Academic Press, London.Google Scholar
  106. Schuber, F., Hong, K., Düzgüneş, N., and Papahadjopoulos, D., 1983, Polyamines as modulators of membrane fusion: Aggregation and fusion of liposomes, Biochemistry 22: 6134–6140.PubMedCrossRefGoogle Scholar
  107. Schullery, S. E., Seder, T. A., Weinstein, D. A., and Bryant, D. A., 1981, Differential thermal analysis of dipalmitoylphosphatidylcholine-fatty acid mixtures, Biochemistry 20:6818–6824.PubMedCrossRefGoogle Scholar
  108. Shimshick, E. J., and McConnell, H. M., 1973, Lateral phase separation in phospholipid membranes, Biochemistry 12:2351–2359.PubMedCrossRefGoogle Scholar
  109. Siegel, D. P., 1984, Inverted micellar structures in bilayer membranes: Formation rates and half-lives, Biophys. J. 45:399–420.PubMedCrossRefGoogle Scholar
  110. Silvius, J. R., and Gagné, J., 1984a, Calcium-induced fusion and lateral phase separations in phosphatidylcholine-phosphatidylserine vesicles. Correlation by calorimetric and fusion measurements, Biochemistry 23:3241–3247.CrossRefGoogle Scholar
  111. Silvius, J. R., and Gagné, J., 1984b, Lipid phase behavior and calcium-induced fusion of phosphatidylethanolamine-phosphatidylserine vesicles. Calorimetric and fusion studies, Biochemistry 23:3232–3240.CrossRefGoogle Scholar
  112. Stewart, T. P., Hui, S. W., Portis, A. R., Jr., and Papahadjopoulos, D., 1979, Complex phase mixing of phosphatidylcholine and phosphatidylserine in multilamellar membrane vesicles, Biochim. Biophys. Acta 556:1–16.PubMedCrossRefGoogle Scholar
  113. Straubinger, R. M., Hong, K., Friend, D. S., and Papahadjopoulos, D., 1983a, Endocytosis of liposomes and intracellular fate of encapsulated molecules: Encounter with A. low pH compartment after internalization in coated vesicles, Cell 32:1069–1079.PubMedCrossRefGoogle Scholar
  114. Straubinger, R. M., Düzgüneş, N., and Papahadjopoulos, D., 1983b, pH-sensitive liposomes: Enhanced cytoplasmic delivery of encapsulated macromolecules, J. Cell Biol.97:109a.Google Scholar
  115. Straubinger, R. M., Hong, K., Friend, D. S., Düzgüneş, N., and Papahadjopoulos, D., 1985a, Endoctyosis of liposomes and intracellular fate of encapsulated molecules: Strategies for enhanced cytoplasmic delivery, in: Receptor-Mediated Targeting of Drugs(G. Greg-oriadis, G. Poste, J. Senior, and A. Trouet, eds.), pp. 297–315, Plenum Press, New York.Google Scholar
  116. Straubinger, R. M., Düzgüneş, N., and Papahadjopoulos, D., 1985b, pH-sensitive liposomes mediate cytoplasmic delivery of encapsulated macromolecules, FEBS Lett. 179:148–154.PubMedCrossRefGoogle Scholar
  117. Strehlow, V., and Jähnig, F., 1981, Electrostatic interactions at charged lipid membranes. Kinetics of the electrostatically triggered phase transition, Biochim. Biophys. Acta 641:301–310.PubMedCrossRefGoogle Scholar
  118. Struck, D. K., Hoekstra, D., and Pagano, R. E., 1981, Use of resonance energy transfer to monitor fusion, Biochemistry 20:4093–4099.PubMedCrossRefGoogle Scholar
  119. Sundler, R., 1984, Role of phospholipid head group structure and polarity in the control of membrane fusion, Biomembranes 12:563–583.Google Scholar
  120. Sundler, R., and Wijkander, J., 1983, Protein-mediated intermembrane contact specifically enhances Ca2+-induced fusion of phosphatidate-containing membranes, Biochim. Biophys. Acta 730:391–394.PubMedCrossRefGoogle Scholar
  121. Sundler, R., Düzgüneş, 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 649:751–758.PubMedCrossRefGoogle Scholar
  122. Takeuchi, Y., and Nikaido, H., 1981, Persistence of segregated phospholipid domains in phospholipid lipopolysaccharide mixed bilayers: Studies with spin-labeled phospholipids, Biochemistry 20:523–529.PubMedCrossRefGoogle Scholar
  123. Tilcock, C. P. S., and Cullis, P. R., 1981, The polymorphic phase behavior of mixed phosphatidylserine-phosphatidylethanolamine model systems as detected by 31P-NMR: Effects of divalent cations and pH, Biochim. Biophys. Acta 641:189–210.PubMedCrossRefGoogle Scholar
  124. Tokutomi, S., Lew, R., and Ohnishi, S. I., 1981, Ca2+-induced phase separation in phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine mixed membranes, Biochim. Biophys. Acta 643:276–282.PubMedCrossRefGoogle Scholar
  125. Träuble, H., and Eibl, H., 1974, Electrostatic effects on lipid phase transitions: Membrane structure and ionic environment, Proc. Natl. Acad. Sci. USA. 71:214–219.PubMedCrossRefGoogle Scholar
  126. Usher, J. R., Epand, R. M., and Papahadjopoulos, D., 1978, The effect of free fatty acids on the thermotropic phase transition of dimyristoyl glycerophosphocholine, Chem. Phys. Lipids 22:245–253.PubMedCrossRefGoogle Scholar
  127. Verkleij, A. J., 1984, Lipidic intramembranous particles, Biochim. Biophys. Acta 779:43–63.PubMedCrossRefGoogle Scholar
  128. 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 555:358–361.PubMedCrossRefGoogle Scholar
  129. 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 HIItransitions, Biochim. Biophys. Acta 600:620–624.PubMedCrossRefGoogle Scholar
  130. Verkleij, A. J., Leunissen-Bijvelt, J., de Kruijff, B, Hope, M., and Cullis, P. R., 1984, Non-bilayer structures in membrane fusion, in: Cell Fusion, Ciba Foundation Symposium 103, pp. 45–59, Pitman Books, London.Google Scholar
  131. Wilschut, J., Düzgüneş, N., Fraley, R., and Papahadjopoulos, D., 1980, Studies on the mechanism of membrane fusion: Kinetics of Ca2+-induced fusion of phosphatidyl-serine vesicles followed by A. new assay for mixing of aqueous vesicle contents, Biochemistry 19:6011–6021.PubMedCrossRefGoogle Scholar
  132. Wilschut, J., Düzgüneş, 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 20:3126–3133.PubMedCrossRefGoogle Scholar
  133. Wilschut, J., Düzgüneş, N., Hoekstra, D., and Papahadjopoulos, D., 1985, Modulation of membrane fusion by membrane fluidity: Temperature dependence of divalent cation-induced fusion of phosphatidylserine vesicles, Biochemistry 24:8–14.PubMedCrossRefGoogle Scholar
  134. Yoshimura, T., and Aki, K., 1985, Sodium-induced aggregation of phosphatidc acid and mixed phospholipid vesicles, Biochim. Biophys. Acta 815:167–1732.Google Scholar
  135. Yoshimura, A., Kuroda, K., Kawasaki, K., Yamashina, S., Maeda, T., and Ohnishi, S. I., 1982, Infectious cell entry mechanism of influenza virus,J. Virol. 43:284–293.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Nejat Düzgüneş
    • 1
  • Keelung Hong
    • 1
  • Patricia A. Baldwin
    • 1
  • Joe Bentz
    • 2
  • Shlomo Nir
    • 3
  • Demetrios Papahadjopoulos
    • 1
  1. 1.Cancer Research Institute, School of Medicine, and Department of Pharmaceutical Chemistry, School of PharmacyUniversity of California at San FranciscoSan FranciscoUSA
  2. 2.Departments of Pharmacy and Pharmaceutical Chemistry, School of PharmacyUniversity of California at San FranciscoSan FranciscoUSA
  3. 3.Seagram Centre for Soil and Water SciencesHebrew University of JerusalemRehovotIsrael

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