The role of nonbilayer lipid structures in the fusion of human erythrocytes induced by lipid fusogens.

(1) A comparative study of the polymorphic phase behaviour of reconstituted erythrocyte phospholipase with 'fusogens' and chemically related 'non-fusogens' using 31P-NMR techniques has been made. We demonstrate that only fusogens can induce a conformational change in the membrane lipids from the bilayer of the hexagonal (HII) phase. (2) The tendency of erythrocyte (ghost) membranes to adopt nonbilayer structures is correlated with the extent of fusion in erythrocytes at various membrane concentrations of glycerol monooleate. Above a certain critical membrane concentration of glycerol monooleate, there is an increase in the tendency of ghost membranes to adopt the HII phase, which is paralleled by a marked increase in fusion processes in the intact erythrocytes. (3) These observations are consistent with a common mechanism of action for fusogenic lipids whereby inverted lipid structures such as long cylinders (HII configuration) or inverted micelles are induced, which serve as intermediates in the fusion event.