title: Structural Origins of Cholesterol Accelerated Lipid Flip-Flop Studied by Sum-Frequency Vibrational Spectroscopy.
abstract: The unique structure of cholesterol and its role in modulating lipid translocation (flip-flop) were examined using sum-frequency vibrational spectroscopy (SFVS). Two structural analogues of cholesterol--cholestanol and cholestene--were examined to explore the influence of ring rigidity and amphiphilicity on controlling distearoylphosphocholine (DSPC) flip-flop. Kinetic rates for DSPC flip-flop were determined as a function of sterol concentration and temperature. All three sterols increased the rate of DSPC flip-flop in a concentration-dependent manner following the order cholestene > cholestanol > cholesterol. Rates of DSPC flip-flop were used to calculate the thermodynamic activation free energy barrier (ΔG(‡)) in the presence of cholesterol, cholestanol, and cholestene. The acyl chain gauche content of DSPC, mean lipid area, and membrane compressibility were correlated to observed trends in ΔG(‡). ΔG(‡) for DSPC flip-flop showed a strong positive correlation with the molar compression modulus (K*) of the membrane, influenced by the type and concentration of the sterol added. Interestingly, cholesterol is distinctive in maintaining invariant membrane compressibility over the range of 2-10 mol %. The results in this study demonstrate that the compression modulus of a membrane plays a significant role in moderating ΔG(‡) and the kinetics of native, protein-free, lipid translocation in membranes.
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112, United States.
authors.forename: John S
authors.initials: JS
authors.lastname: Allhusen
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112, United States.
authors.forename: Dylan R
authors.initials: DR
authors.lastname: Kimball
authors.affiliation: Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112, United States.
authors.forename: John C
authors.initials: JC
authors.lastname: Conboy
mesh_terms: D002784:Cholesterol / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D008051:Lipid Bilayers / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000737:chemistry*; D013057:Spectrum Analysis
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D002784:Cholesterol