What happens if cholesterol is made smoother: Importance of methyl substituents in cholesterol ring structure on phosphatidylcholine-sterol interaction

¹ Institute of Molecular biology and biotechnology
² Department of Biophysics, Jagiellonian University
³ Institute of Physics, Tampere University of Technology, Finland
⁴ The University of Western Ontario

^* To whom correspondence should be addressed. E-mail: mkarttu{at}uwo.ca.

Submitted on August 17, 2006
Revised on September 17, 2006
Accepted on 12 December 2006

	Abstract

While sterols constitute one of the most important molecular species in cells, the reasons for their structure-function relationships in lipid membranes are not well understood. The main objective of this work is to elucidate the recently suggested possibility that the ordering and condensing effects of sterols on phospholipid membranes are related to the smoothness of a sterol. We focus on cholesterol, which has two methyl groups attached to its -face, and compare its properties to the de-methylated cholesterol (Dchol) from which the two methyl groups have been removed. Atomic-scale molecular dynamics simulations of lipid membranes comprised of saturated lipids and sterols, either cholesterol or Dchol, provide compelling evidence that despite its smoother structure, the ordering and condensing effects of Dchol are less effective than those of cholesterol. The ordering capability of both cholesterol and Dchol is highly asymmetric with respect to their ring structure, but while cholesterol favors the -face, Dchol favors the -face. The origin and implications of this difference are analyzed in detail. The picture, which emerges from this study, supports a view that the two methyl groups at the steroid ring system of cholesterol play an important role in cholesterol-lipid interactions by reducing sterol tilt in the bilayer and hence allowing for an optimal orientation for cholesterol.

Key Words: cholesterol, computer simulation, de-methylated cholesterol, lipid membranes, orderding

This article has been cited by other articles:

				H. Martinez-Seara, T. Rog, M. Pasenkiewicz-Gierula, I. Vattulainen, M. Karttunen, and R. Reigada Interplay of Unsaturated Phospholipids and Cholesterol in Membranes: Effect of the Double-Bond Position Biophys. J., October 1, 2008; 95(7): 3295 - 3305. [Abstract] [Full Text] [PDF]

				K. Sabatini, J.-P. Mattila, and P. K. J. Kinnunen Interfacial Behavior of Cholesterol, Ergosterol, and Lanosterol in Mixtures with DPPC and DMPC Biophys. J., September 1, 2008; 95(5): 2340 - 2355. [Abstract] [Full Text] [PDF]