The overall objective of this research is to gain quantitative insight into lipid lipid and lipid-protein interactions in the fluid bilayer state, using a combination of synthetic-organic chemistry, physical-organic chemistry, and the nearest-neighbor recognition method. The long-term goal of this program is to develop a fundamental understanding of the two- dimensional organization of fluid bilayers, which will help to bring exploitable targets in biological membranes (e.g., the plasma membrane of cancer cells, bacterial cells, and fungal cells) into sharper focus. Such insight will assist the rational design of novel classes of therapeutic agents.
The specific aims of the current funding period include: (1) mapping out phase diagrams of sphingolipid/glycerophospholipid/cholesterol, and analogous glycerophospholipid/glycerophospholipid/cholesterol, bilayers by use of nearest-neighbor recognition methods; (2) defining the nearest-neighbor preference of cholesterol with respect to a sphingolipid and a glycerophospholipid; (3) defining the influence of a carbohydrate head group in promoting self-aggregation; (4) testing for transmembrane-protein recognition of a phospholipid based on hydrophobic matching, (5) measuring the sensitivity of lipid transmembrane-protein interactions toward the presence of cholesterol, (6) developing a methodology that can be used to study lipid communication between adjoining monolayers, and (7) detecting transmembrane recognition of neighboring lipids.
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