Specific Spatial and Orientational Order in Phospholipid Membranes Induced by Cholesterol

Abstract

Cholesterol plays a major role in formation of laterally ordered membrane structures such as lipid rafts. These domains have been found to be involved in a variety of cellular functions, implying that there is immediate interest to understand the structure as well as the dynamics of rafts, and in particular the role of cholesterol in promoting order in rafts. Nonetheless, due to the molecular scales associated with lipid rafts and the soft nature of membrane domains overall, the atomic-level mechanisms responsible for cholesterol's specific ordering capability have remained unresolved. Our atomistic simulations [1] reveal that this ordering and the associated packing effects in membranes largely result from cholesterol's molecular structure, which differentiates cholesterol from other sterols. Cholesterol molecules are found to prefer a specific spatial and orientational molecular in-plane organization, where cholesterol molecules are located in the second coordination shell, avoiding direct cholesterol-cholesterol contacts, and forming a three-fold symmetric arrangement with proximal cholesterol molecules. At larger distances, the lateral three-fold organization is broken by thermal fluctuations. Other sterols having less structural asymmetry are found to lack the three-fold arrangement that is characteristic to cholesterol.[1] H. Martinez-Seara, T. Rog, M. Karttunen, I. Vattulainen, and R. Reigada. Manuscript under review (2009).