Effect of Liposomal Composition on Photoactivated Liposome Fusion

Abstract

Bennett and O'Brien [(1995) Biochemistry34, 3102] showed that the ultraviolet light exposure of two-component large unilamellar liposomes (LUV) composed of a 3:1 molar mixture of dioleoylphosphatidylethanolamine (DOPE) and 1,2-bis[10-(2‘-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphatidylcholine (bis-SorbPC) facilitated liposome fusion. The rate and extent of liposome fusion was dependent on the extent of photopolymerization, the temperature, and the pH. Examination of the temperature dependence of fusion of photolyzed and unphotolyzed liposomes demonstrated that an enhancement of the rate of fusion occurred in the temperature range associated with the initial appearance of precursors to the inverted cubic (Q_II) phase [Barry et al. (1992) Biochemistry31, 10114]. Here, the effect of the molar lipid ratio of the DOPE/bis-SorbPC liposomes on the temperature for the onset of fusion, i.e. the critical fusion temperature, was characterized by changing the relative amounts of unreactive polymorphic lipid and reactive lamellar lipid. In each case, photopolymerization of bis-SorbPC lowered the critical fusion temperature by ca. 15−20 °C. The photoreaction of the bis-SorbPC-containing LUV yields cross-linked poly-SorbPC, enhancing the lateral separation of the DOPE and the polylipid and causing isothermal induction of liposome fusion by lowering the temperature for the onset of fusion. Evidence is presented to support the hypothesis that the critical temperature for fusion of two LUV populations depends on the molar ratio of the monomeric lipids in heterodimers of the two LUV. This analysis indicates that the photopolymerization of appropriately designed LUV can decrease the critical fusion temperature from above to below 37 °C.