EFFECTS OF LIPID HEADGROUP AND PACKING STRESS ON POLY(ETHYLENE GLYCOL)-INDUCED PHOSPHOLIPID VESICLE AGGREGATION AND FUSION

The effect of lipid headgroup and curvature-related acyl packing stres s on PEG-induced phospholipid vesicle aggregation and fusion were stud ied by measuring vesicle and aggregate sizes using the quasi-elastic l ight scattering and fluorescence energy transfer techniques. The effec t of the lipid headgroup was monitored by varying the relative phospha tidylcholine (PC) and phosphatidylethanolamine (PE) contents in the ve sicles, and the influence of hydrocarbon chain packing stress was cont rolled either by the relative amount of PE and PC content in the vesic les, or by the degree of unsaturation of the acyl chains of a series o f PEs, e.g., dilinoleoylphosphatidylethanolamine (dilin-PE), lysophosp hatidylethanolamine (lyso-PE), and transacylated egg phosphatidylethan olamine (TPE). The PEG threshold for aggregation depends only weakly o n the headgroup composition of vesicles. However, in addition to the l ipid headgroup, the curvature Stress of the monolayer that forms the v esicle walls plays a very important role in fusion. Highly stressed ve sicles, i.e., vesicles containing PE with highly unsaturated chains, n eed less PEG to induce fusion, This finding applies to the fusion of b oth small unilamellar vesicles and large unilamellar vesicles, The eff ect of electrostatic charge on vesicle aggregation and fusion were stu died by changing the pH of the vesicle suspension media. At pH 9, when PE headgroups are weakly charged, increasing electrostatic repulsion between headgroups on the same bilayer surface reduces curvature stres s, whereas increasing electrostatic repulsion between apposing bilayer headgroups hinders intervesicle approach, both of which inhibit aggre gation and fusion, as expected.