SPONTANEOUS FRAGMENTATION OF DIMYRISTOYLPHOSPHATIDYLCHOLINE VESICLES INTO A DISCOIDAL FORM AT LOW PH

Upon prolonged incubation at low pH, the turbidity of a dimyristoylpho sphatidylcholine (DMPC) small unilamellar vesicle (SUV) suspension und erwent an initial increase followed by a decrease to below the startin g value. Electron microscopic observation of the vesicle suspension, a fter the turbidity minimum was reached, revealed the formation of disc oidal particles which were smaller than the original vesicles. NMR stu dies indicated that all the choline groups in the discoids are accessi ble to added chemical shift agent, corroborating the fragmentation of the vesicles. Formation of the discoids from DMPC multilamellar vesicl e (MLV) was also observed but without going through the initial increa se in turbidity. The DMPC was subsequently found to be hydrolyzed into lysophosphatidylcholine (lysoPC) and myristic acid under the same con ditions that caused the fragmentation. That the discoidal fragment con sisted of DMPC and its hydrolysis products, lysoPC and myristic acid, was verified by electron microscopic observation of discoids when thes e components were mixed at neutral pH. A 50% cholesterol content preve nted the fragmentation of DMPC vesicles. A model for this discoidal co mplex, in which a patch of DMPC bilayer is surrounded at its periphery by lysoPC and myristic acid, is proposed.