Transmembrane distribution of α-tocopherol in single-lamellar mixed lipid vesicles

Summary A study of the molar ratio dependence of the incorporation of -tocopherol into single-lamellar vesicles showed that the number of molecules which the bilayers can accommodate increased linearly with increasing -tocopherol/phosphatidylcholine initial molar ratios till about 0.05, then approached a saturation limit. At 5 mol%, one -tocopherol molecule per 60 phospholipids can be incorporated into the membranes. Up to this limit the distribution of -tocopherol in the bilayers is uniform, while at initial molar ratios higher than 0.05 a disproportionation toward the inner monolayer of the vesicles is observed. The average outer/total ratio is found to be 0.27±0.03 at -tocopherol/phosphatidylcholine molar ratios above 0.07 and is similar to asymmetrical distributions that have been reported in vesicles containing other one-chain amphiphiles (e.g., cholesterol). This large disproportionation is in contrast with the packing distribution of certain twochain amphiphiles, and indicates that one of the driving forces for asymmetry formation in lipid bilayers might be dependent on the number of hydrocarbon chains per amphiphile molecule. A possible reason for the disproportionation effect observed in our experiments is the displacement of unsaturated phospholipids to the outer monolayer of the single-lamellar vesicles, by the more rigid isoprene units of -tocopherol.