EFFECT OF LIPOSOMAL COMPOSITION ON PHOTOACTIVATED LIPOSOME FUSION

Bennett and O'Brien [(1995) Biochemistry 34, 3102] showed that the ult raviolet light exposure of two-component large unilamellar liposomes ( LUV) composed of a 3:1 molar mixture of dioleoylphosphatidylethanolami ne (DOPE) and noyloxy)decanoyl]-sn-glycero-3-phosphatidylcholine (bis- SorbPC) facilitated liposome fusion. The rate and extent of liposome f usion was dependent on the extent of photopolymerization, the temperat ure, and the pH. Examination of the temperature dependence of fusion o f photolyzed and unphotolyzed liposomes demonstrated that an enhanceme nt 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) Biochemistry 31, 10114]. Here, the effect of the molar lipid ratio of the DOPE/bis-SorbPC liposomes on the temp erature for the onset of fusion, i.e. the critical fusion temperature, was characterized by changing the relative amounts of unreactive poly morphic lipid and reactive lamellar lipid. in each case, photopolymeri zation of bis-SorbPC lowered the critical fusion temperature by ca. 15 -20 degrees C. The photoreaction of the bis-SorbPC-containing LUV yiel ds crosslinked poly-SorbPC, enhancing the lateral separation of the DO PE and the polylipid and causing isothermal induction of liposome fusi on by lowering the temperature for the onset of fusion. Evidence is pr esented to support the hypothesis that the critical temperature for fu sion of two LUV populations depends on the molar ratio of the monomeri c 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 degrees C.