Calcium-induced aggregation and fusion of mixed phosphatidylcholine-phosphatidic acid vesicles as studied by 31P NMR.

1. The transbilayer distribution of the phospholipids in sonicated egg phosphatidylcholine-phosphatidic acid vesicles and the interaction of Ca2+ with these vesicles was studied by 31P NMR. 2. Over a wide composition range the bilayer of these vesicles has a symmetrical phospholipid composition. 3. With ratios of Ca2+ to phosphatidic acid in the outer monolayer of the vesicles up to 0.3, Ca2+ induces vesicle aggregation. The extent of aggregation is increased by the Ca2+ concentration in the medium and the outer monolayer concentration of phosphatidic acid. The vesicle aggregation can be fully reversed by chelating Ca2+. 4. When the ratio exceeds 0.5 Ca2+ induces vesicle fusion. The fusion is maximal for vesicles containing both phosphatidylcholine and phosphatidic acid. The data suggest that Ca2+-induced lateral phase separations make the bilayer more susceptible to fusion.