CHANGES IN VESICLE MORPHOLOGY INDUCED BY LATERAL PHASE-SEPARATION MODULATE PHOSPHOLIPASE A(2) ACTIVITY

The action of phospholipase A(2) (PLA(2)) toward zwitterionic bilayers is modulated by lateral phase separation of reaction products and sub strate. The experiments here address the mechanism of this modulation. PLA(2) is particularly active toward lipid dispersions containing rea ction products and substrates in which lateral phase separation has oc curred. Here, we study PLA(2) activity in two related model systems: f irst in a system in which lateral phase separation can be produced a p riori, and second in a system in which the action of PLA(2) produces s ufficient reaction product in situ such that lateral phase separation occurs. The dispersions in which lateral phase separation occurs a pri ori form either disk micelles or disk vesicles, not canonical vesicles . When lateral phase separation occurs due to in situ PLA(2) activity, there is an abrupt change in vesicle structure and a simultaneous pro found increase in catalytic rate. This observation is surprising in li ght of several reports that vesicles remain intact even when the entir e outer monolayer has been hydrolyzed. Membrane curvature and the asso ciated structural defects and dynamic fluctuations in membrane structu re have been proposed to modulate PLA(2) activity. The mechanism by wh ich lateral phase separation modulates PLA(2) activity has been unclea r. The data presented here indicate that lateral phase separation affe cts PLA(2) activity by altering membrane curvature and/or inducing def ects in the membrane structure.