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 micellar2,3 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-workers4–8 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 phases9,10. 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 (HII) 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.