Systematic Relationship between Phospholipase A2 Activity and Dynamic Lipid Bilayer Microheterogeneity

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Abstract
A standing hypothesis in membrane biology implies that the collective physical properties of the lipid bilayer component of biological membranes can modulate the activity of membrane-associated proteins. We provide strong support for this hypothesis by exploring a model system, phospholipase A2 catalyzed hydrolysis of one-component phospholipid vesicles. For vesicles of lipids with different chain lengths we observe, as a function of temperature and chain length, a systematic variation of the characteristic lag time for the onset of rapid phospholipase A2 hydrolysis. These results, combined with theoretical results obtained from computer simulation of the gel-to-fluid phase transition in the unhydrolyzed lipid bilayers, enable us to demonstrate a strong correlation between the lag time and the degree of bilayer microheterogeneity in the phase transition region. Insight into the nature of this correlation suggests rational ways of modulating enzyme activity by modifying the physical properties of the lipid bilayer.