Polymerized Bicontinous Cubic Lipid Assemblies

9523297 O‘Brien由于人们对非片层结构可能的生物学功能感兴趣，近年来，生物和模型类脂膜中非片层结构的形成得到了广泛的研究。在一定的温度和浓度条件下，极性脂形成几何复杂的液晶结构。这些非片层相包括双连续立方相(QII)和倒六方相(HII)。无论非片层相的生物学意义是什么，很明显，稳定的非片层结构提供了新的技术材料，在我们研究非片层相聚合的头两年中，我们成功地展示了一种稳定它们的策略。因此，继续研究的目标是利用这一经过验证的策略来制备一系列稳定的QII和HII相，以保持脂质和水相网络并保持其界面的生物相容性。为了实现这些目标，研究将涉及新的可聚合脂质的设计和合成，水合未聚合脂质组装体的相行为的表征，以及脂类在非片层相中的控制聚合，并仔细注意聚合物的性质，即聚合物链的位置和大小，以及聚合物的交联度。然后将确定聚合的非片层组件的相行为和稳定性。非片层相的稳定方式将扩大温度和浓度的范围，有利于所需的非片层结构的存在，并增加组装件对表面活性剂或有机溶剂溶解的抵抗力。这项研究将为研究人员提供新的生物材料来探索脂质-水组件的物理和化学。由于已知的几个QII相在对称性和水溶液通道的大小上有所不同，因此可聚合脂类将被设计成形成每个常见基团的QII相，以便生成一系列稳定的有机沸石。QII相的相互渗透网络暗示了这些有机沸石的潜在应用，它们充分利用脂膜表面来定位试剂、固定化抗体片段或抗酶、或结合蛋白质用于化学或生物转化、诊断和/或分离应用。聚合的HII相有望提供规则的六角形阵列，其孔径大小在非常理想的约3到8 nm的范围内，即大到足以允许球形蛋白质或水溶性无规卷曲聚合物的流动。这项研究将为非层状组件的技术利用提供科学依据。这项研究将寻求对高分子链的形成、位置和性质对非片层相特征的影响提供一致的理解。***

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. ***