Direct Measurements of Cholesterol’s Impact on Lipid Hydration and Packing in Phosphatidylcholine Lipid Bilayers

The role of cholesterol in physiological and model biological membranes has been studied extensively. A particularly active research area is the importance of cholesterol in modulating lipid rafts domains, which are thought to be involved in a myriad of cellular processes from protein sorting to signal transduction. Fundamental biophysical studies on model systems have begun to tease out the thermodynamics and molecular level interactions between cholesterol and lipids. In this work, high resolution x-ray diffraction from single supported bilayers and monolayers at the air water interface of phosphatidylcholine-cholesterol mixtures clearly elucidates cholesterol-lipid complex formation, phase separation, and suggests the formation of a cholesterol superlattice with a specific stoichiometric ratio that occurs in lipid bilayers but not in the lipid monolayers. Importantly, convincing evidence will be presented that cholesterol alters the hydration of saturated phosphatidylcholine lipid bilayers, resulting in significant changes in lipid packing and orientation.