Curvature and composition-dependent lipid asymmetry in phosphatidylcholine vesicles containing phosphatidylethanolamine and gangliosides.

The effect of curvature on transbilayer lipid asymmetry in vesicles is investigated using vesicles of different sizes (30-140 nm) prepared by sonication and polycarbonate filter extrusion techniques. The transbilayer distributions of phosphatidylethanolamine and gangliosides are measured using 2,4,6-trinitrobenzenesulphonic acid and Clostridium perfringens neuraminidase as non-penetrating probes, respectively. The distribution of phosphatidylethanolamine in a phosphatidylcholine/phosphatidylethanolamine (4:1, molar ratio) system is more or less symmetric and curvature seems to have little effect. However, the distribution of gangliosides in a phosphatidylcholine/ganglioside (10:1, molar ratio) system is asymmetric in favour of the outer layer in smaller vesicles, the asymmetry disappearing as the degree of curvature decreases. In a phosphatidylcholine/phosphatidylethanolamine/ganglioside (8:2:1, molar ratio) system, both phosphatidylethanolamine and gangliosides distribute asymmetrically, indicating a composition-dependent asymmetric distribution of phosphatidylethanolamine. In this system asymmetry also increases with increasing curvature. The asymmetric distribution of gangliosides in vesicles of low curvature may be due to their long headgroup and larger headgroup surface area in accordance with the theoretical predictions of Israelachvili et al. (Biochim. Biophys. Acta 470 (1977) 185-201).