Comparing the Biophysical Properties of Sterols in Lipid Membranes – What Is Special about Cholesterol? Holger A. Scheidt 1,3,4 , Peter Müller 2 , Andreas Herrmann 2 , Klaus Arnold 3 , Klaus Gawrisch 4 , Daniel Huster 1,3 1 Junior Research Group "Solid-State NMR Studies of the Structure of Membrane- associated Proteins", Biotechnological-Biomedical Center, University Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany scheh@medizin.uni.leipzig.de 2 Institute of Biology/Biophysics Humboldt-University Berlin, Germany 3 Institute of Medical Physics and Biophysics, University of Leipzig, Germany 4 National Institute of Alcohol Abuse and Alcoholism / National Institute of Health, Rockville, MD, USA 1. Introduction Cholesterol is a major constituent of mammalian cell membranes. Its biophysical properties are essential for several membrane functions. However, a recently described generation of knock out mice, entirely lacking cholesterol [1], showed surprisingly mild phenotype changes. Since the cell membranes of these mice contained desmosterol, the direct precursor of cholesterol, we compared the biophysical properties of membranes containing cholesterol, desmosterol and lanosterol (a more distant precursor). d phenotype changes. Since the cell membranes of these mice contained desmosterol, the direct precursor of cholesterol, we compared the biophysical properties of membranes containing cholesterol, desmosterol and lanosterol (a more distant precursor). 2. Membrane packing Membrane packing properties were studied by 2 H NMR, fluorescence, and EPR spectroscopy. It was found that cholesterol and desmosterol showed a very similar behavior, while lanosterol produced significantly weaker effects [2]. 3. Lateral Diffusion We also investigated the effect of the sterols on the lateral diffusion of the lipids and of the sterols, respectively, by 1 H PFG MAS NMR spectroscopy. In the liquid-crystalline phase, the phospholipid diffusion coefficients are decreased in the presence of all three sterols. In the l o -phase this decrease strongly depends on the cholesterol concentration. Cholesterol mirrors the lipid behavior, but exhibits a slightly faster diffusion. In the lanosterol and desmosterol containing membranes, the lipid diffusion rates are somewhat © 2005, H. A. Scheidt The Open-Access Journal for the Basic Principles of Diffusion Theory, Experiment and Application Diffusion Fundamentals 2 (2005) 132.1 - 132.2 1