Effects of fusogenic agent on membrane structure of erythrocyte ghosts and the mechanism of membrane fusion

Abstract

MEMBRANE fusion clearly requires that participating lipids assume some transitory non-bilayer configuration during the intermediate stages. Previous workers have suggested that intermediate micellar¹ or inverted micellar^2,3 structures may occur, but the precise nature of possible intermediates and their relation to the physical properties of membrane lipids are obscure. In this regard, Lucy and co-workers^4–8 have shown that ‘fusogenic’ agents such as fatty acids and their derivatives induce erythrocytes to fuse. Such agents might possibly promote fusion by enabling endogenous lipids to assume non-bilayer configurations. We have therefore investigated the influence of two such fusogens on the structure of the erythrocyte (ghost) membrane using ³¹P NMR techniques, which have been found to be sensitive to phospholipids in non-bilayer phases^9,10. We show that the incorporation of oleic acid and glycerol mono-oleate into the ghost membrane, at concentrations similar to those needed to induce cell fusion between erythrocytes in vitro, produce a well-defined transition of a variable portion of the membrane phospholipids from the bilayer phase to an hexagonal (H_II) phase. These results lead us to propose a model for membrane fusion induced by oleic acid, which we suggest may also apply to fusion events in vivo.