Lipid unsaturation influences melittin-induced leakage of vesicles

Investigation of vesicles composed of different phosphatidylcholines revealed that the extent of leakage of internal contents induced by the lytic agent melittin can range from practically none to essentially complete, depending upon the fatty acyl chain composition of the phospholipid. The extent of leakage increases with the number of double bonds in the series dioleoylphosphatidylcholine < dilinoleoylphosphatidylcholine < dilinolenoylphosphatidylcholine. It depends on the length of the saturated chain with 1-myristoyl-2-arachidonoylphosphatidylcholine vesicles being more sensitive to melittin induced leakage than 1-palmi-toyl-2-arachidonoylphosphatidylcholine, 1-stearoyl-2-arachidonoylphosphatidylcholine or 1-palmitoyl-2- docosahexaenoylphosphatidylcholine vesicles. The extent of leakage induced by melittin from vesicles composed of 1-palmitoyl-2-oleoylphosphatidylcholine, dioleoylphosphatidylcholine, 1-palmitoyl-2-arachidonoylphosphatidylcholine and 1-palmitoyl-2-docosahexaenoyl-phosphatidylcholine increases with the free volume parameter of these lipids for 1,6-diphenylhexatriene (Straume, M. and Litman, B.J. (1987) Biochemistry 26, 5113-5120). Among the lipid examined here, diphytanoylphosphatidylcholine vesicles were least susceptible to melittin induced leakage. The results indicate that lipid fatty acyl structure may be important in lipid-protein interactions of the kind simulated by melittin.