In order to improve our understanding at the molecular level of how lipid organization determines membrane function, experiments are described to analyze lipid-lipid and lipid-protein interactions using spectral, kinetic, and permeability methods. For many of these studies, a series of phosphatidylcholine and sphingomyelin analogs will be synthesized. Special attention will be given to the preparation of compounds differing in the structure of the interfacial region. These analogs will be used to examine the importance of specific sites in the interactions between phospholipids, cholesterol, and proteins and in the rates of lipid movement between membranes. The properties of unusual, naturally occurring ether-linked phospholipids will also be studied. These studies are relevant to an understanding of the structures of both normal membranes and of membranes associated with several disease processes, such as atherosclerosis, where lipid accumulation takes place.
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