LIPID BILAYER STRUCTURE: EFFECT OF SMALL MOLECULES

建议进行一系列结构研究，以获得关于 脂双分子层与三种主要成分的相互作用 生物膜--水、胆固醇和碳水化合物。这些X射线 衍射、中子衍射和冷冻断口电子显微镜 实验的目的是给出关于这些影响的准确细节 分子具有双层结构，特别是在界面上 并帮助确定它们在膜中的功能作用。我们的 实验应该提供与分子机制相关的数据 膜转运过程、细胞聚集、细胞黏附与细胞 核聚变。其中一个项目将重点放在充分渗透水的深度上。 水合双分子膜及其对胆固醇和其他生物效应的影响 活性分子，如麦角甾醇和根癌素有 水/双层界面。第二个项目是试验性地测试两个 排斥力的主要理论模型。这股力量， 它存在于所有药物与受体的相互作用以及所有细胞之间 薄膜，将通过测量之间的力和距离进行分析 在非电解质存在的情况下形成的双分子膜 尺寸和介电性能都比水好。长距离的吸引力 力将以类似的方式进行研究，以确定利夫希茨 形式主义可以令人满意地解释所有长期吸引人的相互作用 在膜之间。此外，我们还建议研究一种新的 反常的片层相，其中相对单层的碳氢链 相互穿透或交错。这一阶段在测试中将非常有用 排斥力和吸引力的理论模型，因为 交指相的每个分子的面积是正常片层的两倍。 相位。

A series of structural studies is proposed to obtain information on the interaction of lipid bilayers with three of the principal components of biological membranes--water, cholesterol, and carbohydrates. These X-ray diffraction, neutron diffraction and freeze-fracture electron microscopy experiments are designed to give precise details concerning effects these molecules have on bilayer structure, particularly in the interfacial region, and to help characterize their functional roles in membranes. Our experiments should provide data relevant to the molecular mechanisms of membrane transport processes, cell aggregation, cell adhesion and cell fusion. One project will focus on the depth of water penetration in fully hydrated bilayers and the influence that cholesterol and other biologically active molecules, such as ergosterol and phloretin, have on the water/bilayer interface. A second project is to experimentally test two major theoretical models of the repulsive hydration force. This force, which is present in all drug-receptor interactions and between all cell membranes, will be analyzed by measuring the force and distance between bilayers in the presence of non-electrolytes which have different dimensions and dielectric properties than water. The long-range attractive force will be studied in a similar manner to determine whether the Lifshitz formalism can satisfactorily explain all long-range attractive interactions between membranes. In addition we propose to study the properties of an unusual lamellar phase where the hydrocarbon chains of apposing monolayers interpenetrate or interdigitate. This phase will be very useful in testing theoretical models for the repulsive and attractive forces, since the interdigitated phase has twice the area per molecule of a normal lamellar phase.