Spontaneous fragmentation of dimyristoylphosphatidylcholine vesicles into a discoidal form at low pH

Upon prolonged incubation at low pH, the turbidity of a dimyristoylphosphatidylcholine (DMPC) small unilamellar vesicle (SUV) suspension underwent an initial increase followed by a decrease to below the starting value. Electron microscopic observation of the vesicle suspension, after the turbidity minimum was reached, revealed the formation of discoidal particles which were smaller than the original vesicles. NMR studies indicated that all the choline groups in the discoids are accessible to added chemical shift agent, corroborating the fragmentation of the vesicles. Formation of the discoids from DMPC multilamellar vesicle (MLV) was also observed but without going through the initial increase in turbidity. The DMPC was subsequently found to be hydrolyzed into lysophosphatidylcholine (lysoPC) and myristic acid under the same conditions that caused the fragmentation. That the discoidal fragment consisted of DMPC and its hydrolysis products, lysoPC and myristic acid, was verified by electron microscopic observation of discoids when these components were mixed at neutral pH. A 50% cholesterol content prevented the fragmentation of DMPC vesicles. A model for this discoidal complex, in which a patch of DMPC bilayer is surrounded at its periphery by lysoPC and myristic acid, is proposed.