Comparative Molecular Dynamics Study of Lipid Membranes Containing Cholesterol and Ergosterol

¹ Gdansk University of Technology

^* To whom correspondence should be addressed. E-mail: maciekb{at}hypnos.chem.pg.gda.pl.

Submitted on August 18, 2005
Revised on October 6, 2005
Accepted on 16 November 2005

	Abstract

Sterol molecules are essential for maintaining the proper structure and function of eukaryotic cell membranes. The influence of cholesterol (the principal sterol of higher animals) on the lipid bilayer properties was extensively studied by both experimental and simulation methods. In contrast, the effect of ergosterol (the principal fungal sterol) on the membrane structure and dynamics is much less recognized. The current work presents the results of comparative molecular dynamics simulation of the hydrated dimyristoylphosphatidylcholine (DMPC) bilayer containing ~25 mol % of cholesterol or ergosterol. A detailed analysis of the molecular properties (e.g., bilayer thickness, lipid order, diffusion, intermolecular interactions etc.) of both sterol-induced liquid-ordered membrane phases is presented. Presence of sterols in the membrane changes significantly its property, especially fluidity and molecular packing. Moreover, in accordance with the experiments our calculations show that, compared to cholesterol, ergosterol has higher ordering effect on the phospholipid acyl chains. This different influence on the properties of the lipid bilayer stems from differences in conformational freedom of sterol side chains. Additionally, obtained models of lipid membranes containing human and fungal sterols, constituting result of our work, can be also utilized in other chemotherapeutic studies on interaction of selected ligands (e.g., antifungal compounds) with membranes.

Key Words: lipid bilayer, liquid-ordered phase, molecular simulation of membranes, phospholipid membranes, sterols

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