SHORT- AND LONG-RANGE FORCES BETWEEN MEMBRANCE SURFACES

这个应用程序的总体目标是衡量和描述三个 基本的、非特定的相互作用 水中的大分子组装。的大小和范围 将测量水合作用、空间位阻和波动排斥压力。 X-射线衍射法研究脂质双层膜之间的相互作用 渗透压下的脂质体。将使用电子密度分布 要在每次应用时获得双层的中等分辨率视图 渗透压。本研究选用双层膜作为研究对象。 有两个原因。第一，组成、结构、内聚性和 膜的静电势可以精确控制，因此 每个排斥力的关键物理参数可以是 对其来源进行了调查和模型测试。例如， 可以检验的假设是，水合压力是由 层间水在电场作用下的极化。双层的。 其次，膜表面之间的相互排斥作用是至关重要的。 在许多生理过程中。特别是，这些压力将是 对含有各种糖脂或含有脂类的双层进行测量 与共价连接的聚乙二醇组分。因为糖脂 被认为介导了细胞与其细胞之间的许多相互作用 环境中，设计实验来确定结构和 膜中糖脂的相互作用性质。聚乙二醇脂延展 脂质体的血液循环时间，从而使药物输送到 实体瘤。实验的目的是测试这一假设 循环时间的增加是由于 聚乙二醇脂。拟议中的实验也旨在增加立体结构。 通过改变双层基质的内聚性来阻挡。 其他技术将用于解决这些假设并获得 尽可能完整地描述三种界面作用力 主要包括：(1)用吸水等温线测定含水率 膜与水化能，(2)微吸管操作 单壁小泡的粘附能和凝聚力 膜的性质，(3)渗透胁迫实验 温度提供热焓和熵的函数 组分压力的贡献，(4)表面和Zeta电位 获得双层电场的测量，(5)表面压力-面积 单分子层等温线，以获得平面内相互作用 (6)差示扫描量热法测定相组成 含有聚乙二醇脂类的双层膜的行为。

The overall goal of this application is to measure and characterize three fundamental, non-specific interactions that operate between macromolecular assemblies in water. The magnitude and range of the hydration, steric, and undulation repulsive pressures will be measured between lipid bilayer membranes by x-ray diffraction analysis of osmotically stressed liposomes. Electron density profiles will be used to obtain a moderate resolution view of the bilayer at each applied osmotic pressure. Bilayer membranes have been chosen for this study for two reasons. First, the composition, structure, cohesive properties, and electrostatic potential of the membranes can be precisely controlled so that key physical parameters of each repulsive pressure can be investigated and models for their origin tested. For example, the hypothesis win be tested that the hydration pressure is caused by the polarization of interlamellar water by electric fields of the. bilayer. Second, the repulsive interactions between membrane surfaces are critical in many physiological processes. In particular, these pressures will be measured for bilayers containing various glycolipids or containing lipids with covalently attached polyethylene glycol (PEG). Since glycolipids are thought to mediate many interactions of cells with their surroundings, experiments are designed to determine the structure and interactive properties of glycolipids in membranes. PEG-lipids extend blood Circulation time of liposomes, thereby allowing drug delivery to solid tumors. Experiments are designed to test the hypothesis that this increased circulation time is due to steric stabilization caused by the PEG-lipid. Proposed experiments are also aimed at increasing the steric barrier by modifying the cohesive properties of the bilayer matrix. Other techniques that will be used to address these hypotheses and obtain as complete a picture as possible of the three intersurface forces include: (1) water adsorption isotherms to determine the water content of the membrane and the energy of hydration, (2) micropipette manipulation of single-walled vesicles to obtain the adhesion energy and the cohesive properties of the membrane, (3) osmotic stress experiments performed as a function of temperature to provide the enthalpic and entropic contributions of the component pressures, (4) surface and zeta potential measurements to obtain bilayer electric fields, (5) surface pressure-area monolayer isotherms to obtain the in-plane interactions between the PEG-lipids, and (6) differential scanning calorimetry to obtain the phase behavior of bilayers containing PEG-lipids.