THE RELATIONSHIP BETWEEN COMPOSITIONAL PHASE-SEPARATION AND VESICLE MORPHOLOGY - IMPLICATIONS FOR THE REGULATION OF PHOSPHOLIPASE A(2) BY MEMBRANE-STRUCTURE

The action of phospholipase A(2) (PLA(2)) on bilayer substrates causes the accumulation of reaction products, lyso-phospholipid and fatty ac id. These reaction products and the phospholipid substrate generate co mpositional heterogeneities and then apparently phase separate when a critical mole fraction of reaction product accumulates in the membrane . This putative phase separation drives an abrupt morphologic rearrang ement of the vesicle, which may be in turn responsible for modulating the activity of PLA,. Here we examine the thermotropic properties of t he phase-separated lipid system formed upon hydrating colyophilized re action products (1:I palmitic acid:1-palmitoyl-2-lyso-phosphatidylchol ine) and substrate, dipalmitoylphosphatidylcholine. The mixture forms structures which are not canonical spherical vesicles and appear to be disks in the gel-state. The main gel-liquid transition of these struc tures is hysteretic. This hysteresis is apparent using several techniq ues, each selected for its sensitivity to different aspects of a lipid aggregate's structure. The thermotropic hysteresis reflects the coupl ing between phase separation and changes in vesicle morphology. (C) 19 97 Elsevier Science Ireland Ltd.