9523297 O'Brien The formation of nonlamellar lipid structures in biological and model lipid membranes has been extensively investigated in recent years, because of the interest in the possible biological function of nonlamellar structures. At certain conditions of temperature and concentration polar lipids form geometrically complex liquid crystalline structures. These nonlamellar phases include bicontinuous cubic phases (QII) and the inverted hexagonal phase (HII). Whatever may be the biological significance of nonlamellar phases, it is clear that stabilized nonlamellar structures offer novel technological materials, In the first two years of our research into the polymerization of nonlamellar phases we have successfully demonstrated a strategy for their stabilization. The objective then of the continuing research is to utilize this proven strategy to prepare a family of stabilized QII as well as HII phases in a manner that preserves both the lipid and aqueous phase networks and retains the biocompatibility of their interface. In order to accomplish these goals the research will involve the design and synthesis of new polymerizable lipids, the characterization of the phase behavior of the hydrated unpolymerized lipid assemblies, and the controlled polymerization of the lipids in nonlamellar phases with careful attention to the nature of the polymer, i.e. the location and size of the polymer chains, and the extent of polymer crosslinking. The phase behavior and stability of the polymerized nonlamellar assemblies will then be determined. The nonlamellar phases will be stabilized in a manner that extends the range of temperatures and concentrations that favor the existence of the desired nonlamellar structure, as well as increases the resistance of the assembly to dissolution by surfactants or organic solvents. This research will provide researchers with novel biomaterials to probe the physics and chemistry of lipid-water assemblies. Since several QII phases are known that vary in sy mmetry and the size of the aqueous channels, therefore polymerizable lipids will be designed to form QII phases of each of the commonly found groups in order to generate a family of stabilized organic zeolites. The interpenetrating networks of the QII phase suggests potential applications of these organic zeolites, which take full advantage of the lipid membrane surface for the localization of reagents, the immobilization of antibody fragments or abenzymes, or the incorporation of proteins for chemical or biological conversions, diagnostics, and/or separation applications. Polymerized HII phases are expected to provide regular hexagonal arrays with uniform pore sizes in the highly desirable ca. 3 to 8 nm diameter range, i.e. large enough to permit the flow of globular proteins or water soluble random coil polymers. The proposed research will provide a scientific basis for the technological utilization of nonlamellar assemblies. The research will seek to provide a coherent understanding of the effect of the formation, location, and nature of polymer chains on the characteristics of nonlamellar phases. ***
