COLL 86

Unequal affinity between lipids has been hypothesized to be a mechanism for the formation of microdomains/rafts in membranes. Our studies focus upon the interaction of cholesterol with PUFA (polyunsaturated fatty acid)-containing phospholipids. They support the proposal that steric incompatibility of the rigid steroid moiety for highly disordered PUFA chains, in particular DHA (docosahexaenoic acid, 22:6), provides a sensitive trigger for lateral segregation of lipids into PUFA-rich/sterol-poor and PUFA-poor/sterol-rich regions. Solid state ²H NMR and X-ray diffraction demonstrate that the solubility of cholesterol is low in polyunsaturated bilayers. In mixed membranes of PE (phosphatidylethanolamine) with the lipid raft forming molecules SM (sphingomyelin) and cholesterol, diminished affinity of the sterol for 16:0-22:6PE (1-palmitoyl-2-docosahexaenoylphosphatidylethanolamine) relative to 16:0-18:1PE (1-palmitoyl-2-oleoylphosphatidylethanolamine) is identified by ²H NMR order parameters and detergent extraction. Phase separation of PUFA-containing phospholipid from SM/cholesterol rafts is the implication, which may be associated with the myriad of health benefits of dietary PUFA.