Long chain esters of cholesterol are very nonpolar lipids which, along with triglycerides, are mostly localized in bulk lipid phases like the cores of lipoproteins or arterial lipid deposits. These lipid droplets are separated from surrounding water by a monomolecular layer of amphipathic lipids which constitutes the site of cholesteryl ester mobilization. The long term goal of the project is to understand how the state and concentration of cholesteryl esters in interfaces is regulated by the composition and state of other lipid molecules in the bulk and surface phases. The immediate goals of this project are to understand how cholesteryl ester concentration and state is regulated in planar lipid films at the air/water interface and what regulates the partitioning of cholesteryl esters between these surfaces and bulk lipid phases. This is approached first by measurement and qualitative analysis of the composition dependence of the surface behavior of cholesteryl ester-containing mixtures. Based on these results mathematical models are derived and tested with the goal of understanding and predicting lipid phase distribution and state. Building on our existing knowledge we will determine on what basis different cholesteryl esters occupy available sites at the interface, i.e. how they compete with each other when partitioning from a bulk lipid phase. We will also study the competition between triglycerides and cholesteryl esters for the surface. Related to this will be investigations of the role of the physical state of the bulk phase and miscibility of components in regulating their availability at the surface. To model the effects of the adsorption of proteins and other water soluble constituents to the interface, we will study bile salt interactions with cholesteryl ester-containing films. These studies have direct relevance to cardiovascular pathogenesis and will provide a physical basis for the development of enzymatic techniques to remove arterial lipid deposits.
