Membrane fusion in vesicles of oligomerizable lipids

Membrane fusion has been examined in a model system of small unilamellar ve sicles of synthetic lipids that can be oligomerized through the lipid headg roups. The oligomerization can be induced either in both bilayer leaflets o r in the inner leaflet exclusively. Oligomerization leads to denser lipid h eadgroup packing, with concomitant reduction of lipid lateral diffusion and membrane permeability. As evidenced by lipid mixing assays, electron micro scopy, and light scattering, calcium-induced fusion of the bilayer vesicles is strongly retarded and inhibited by oligomerization. Remarkably, oligome rization of only the inner leaflet of the bilayer is already sufficient to affect fusion. The efficiency of inhibition and retardation of fusion criti cally depend on the relative amount of oligomeric lipid present, on the con centration of calcium ions, and on temperature. Implications for the mechan ism of bilayer membrane fusion are discussed in terms of lipid lateral diff usion and membrane curvature effects.