1. The ability of a number of carboxylic acids, their esters, retinol and α-tocopherol to induce fusion of hen erythrocytes in vitro was investigated. 2. Some 30 different fat-soluble substances (100μg/ml) were found to cause the formation of multinucleated erythrocytes with a suspension of 3×108 erythrocytes/ml. The most effective agents induced fusion within 5–10min at 37°C; some substances required about 1h. 3. Inclusion of Dextran 60C in the test medium minimized colloid osmotic lysis caused by exogenous lipids that induce cell fusion. 4. Cell swelling, followed by cell adhesion, was then seen to precede cell fusion. 5. Fusion occurred with C10–C14 saturated carboxylic acids, with unsaturated, longer-chain carboxylic acids and their mono-esters; retinol, and to a lesser extent α-tocopherol, also caused cell fusion. 6. C6–C9, C15, C16 and C18 saturated carboxylic acids did not induce fusion within 4h; glyceryl dioleate was only weakly active, and glyceryl trioleate was inactive in the test system. 7. Fusion was facilitated by a high ratio of chemical agents to cell number and by incubation between pH5 and 6. It was inhibited by EDTA and by serum albumin. 8. Glyceryl mono-oleate caused both a similar fusion of several species of mammalian erythrocyte and the interspecific fusion of human and chicken erythrocytes. 9. The term ‘fusogenic’ is proposed to describe chemical, viral and physical agents that cause membranes to fuse. 10. The biochemical mechanisms involved and the possible biological significance of membrane fusion by fusogenic lipids are discussed.

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