Evidence for the "cold fusion" of bilayer membranes

Polymerization of the lipid headgroups inhibits calcium-induced fusion of small unilamellar vesicles of the lipid di-n-dodecyloxypropyl beta-nitrostyryl phosphate but does not influence vesicle aggregation. Addition of a copolymer of lauryl methacrylate and acrylamide (LMPAM) provides the vesicles with a steric shield that prevents both fusion and aggregation. Accurate microcalorimetric determination of the enthalpies of vesicle aggregation and fusion was possible by comparison of titrations of vesicles into CaCl2 in the absence and presence of LMPAM, both before and after polymerization of the lipids in the vesicles. Whereas calcium-induced aggregation is associated with an enthalpy of +2.6 +/- 0.1 kJ/mol of Lipid, fusion occurs with a minimal endothermic heat effect. We contend that the driving force of membrane fusion is of entropic origin.