Thermodynamic comparison of the interactions of cholesterol with unsaturated phospholipid and sphingomyelins

¹ Biozentrum Basel
² Biozentrum

^* To whom correspondence should be addressed. E-mail: heiko.heerklotz{at}unibas.ch.

Submitted on December 27, 2005
Revised on January 20, 2006
Accepted on 3 March 2006

	Abstract

A comparative analysis of the interaction of cholesterol (chol) with palmitoyl-oleoyl-phosphatidylcholine (POPC) and sphingomyelins (SM) was performed in largely homogeneous,fluid phase membranes at 50 °C. To this end three independent assays for isothermal titration calorimetry (ITC) were applied to POPC/SM/cho mixtures. Cholesterol is solubilized by randomly methylated--cyclodextrin (cyd) and the uptake of cho into (or release from) large unilamellar vesicles is measured. The affinity of chol to a POPC/SM (1:1)membrane with 30 mol% chol is about 2x higher than to POPC alone; extrapolation to pure SM yields an affinity ratio of R_K - 5. Bringing chol in contact with SM is highly exothermic (-7 kJ/mol for POPC/SM (1:1), and -13 kJ/mol extrapolated to pure SM, both compared to POPC). No pronounced differences were observed between egg, bovine brain, and palmitoyl SM. With decreasing chol content, R_K increases and H becomes more exothermic, suggesting a trend towards superlattice formation. That SM/chol-interactions are enthalpically favourable implies that the preference of chol for SM increases upon cooling and can induce domain formation below a certain temperature. The enthalpy gain is partially compensated by a loss in entropy in accordance with the concept of chol-induced chain ordering, which improves intermolecular interactions (van der Waals, H-bond) but reduces conformational and motional freedom. The ability of Cyd to extract sphingomyelin from membranes is twofold weaker than for POPC.

Key Words: cyclodextrin, enthalpy, isothermal titration calorimetry, lipid rafts

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