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Cholesterol shows preference for the interior of polyunsaturated lipid membranes.

Marrink SJ, de Vries AH, Harroun TA, Katsaras J, Wassall SR

Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands. s.j.marrink@rug.nl

Recent neutron scattering experiments showed a striking manifestation of the aversion between polyunsaturated fatty acid (PUFA)-containing lipids and cholesterol. Selectively deuterated cholesterol/ 1,2-diarachidonylphosphatidylcholine (DAPC) samples revealed that the hydroxyl of the sterol resides at the center of the bilayer. Here we use a recently parametrized coarse grain simulation model to shed light on these puzzling experimental observations. Using a simulation setup in close correspondence to the experimental conditions, we reproduce the experimental neutron scattering profiles to a large extent. The simulations allow us to analyze the behavior of cholesterol in detail; we show that the interaction of cholesterol with the PUFA chains of DAPC leads to a fast flip-flop rate for the sterol and an increased preference of the sterol for the unusual location embedded between the monolayer leaflets.

Published 2 January 2008 in J Am Chem Soc, 130(1): 10-1.
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