SYSTEMATIC RELATIONSHIP BETWEEN PHOSPHOLIPASE A(2) ACTIVITY AND DYNAMIC LIPID BILAYER MICROHETEROGENEITY

A Standing hypothesis in membrane biology implies that the collective physical properties of the lipid bilayer component of biological membr anes can modulate the activity of membrane-associated proteins, We pro vide strong support for this hypothesis by exploring a model system, p hospholipase A(2) catalyzed hydrolysis of one-component phospholipid v esicles, For vesicles of lipids with different chain lengths we observ e, as a function of temperature and chain length, a systematic variati on of the characteristic lag time for the onset of rapid phospholipase A(2) hydrolysis. These results, combined with theoretical results obt ained from computer simulation of the gel-to-fluid phase transition in the unhydrolyzed lipid bilayers, enable us to demonstrate a strong co rrelation between the lag time and the degree of bilayer microheteroge neity in the phase transition region, Insight into the nature of this correlation suggests rational ways of modulating enzyme activity by mo difying the physical properties of the lipid bilayer.