Cholesterol is a major constituent of cellular membranes which controls membranes fluidity, solubilization of immiscible lipid components and has even been implicated in the formation of lipid rafts.  Although our understanding of the structural role cholesterol plays in lipid membranes has been studied extensively, the effect cholesterol has on the transbilayer diffusion or flip-flop of lipid species is not well understood.  We have previously shown that cholesterol increases the rate of flip-flop for the saturated lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) in a concentration dependent manner.  The current study explores the chemical and physical origins which allow cholesterol to radically modulate the native rate of lipid translocation in membranes.  These studies were conducted using the nonlinear technique of sum-frequency vibrational spectroscopy, which allows for the direct detection of lipid flip-flop dynamics.  Several analogues of cholesterol are examined and their effect on the kinetics and thermodynamics of DSPC flip-flop will be discussed, with particular attention paid to 5a-cholestan-3b-ol (cholestanol) and 5-cholestene (cholestene).  Cholestenol lacks a double bond between carbons 5 and 6 which alters the conformation of the sterol rings and cholestene lacks the hydroxyl group on the C3 carbon, changing the lipophilicity of the molecule.  The effect of these chemical and structural changes on the activation thermodynamics for DSPC flip-flop will be discussed in detail.<br/>

Molecular origins of cholesterol accelerated lipid flip-flop

251st National Meeting (2016)

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