SHORT- AND LONG-RANGE FORCES BETWEEN MEMBRANCE SURFACES

该应用程序的总体目标是测量和表征三个 基本的，非特定的相互作用， 大分子聚合物 的幅度和范围 将测量水化、空间位阻和波动排斥压力 通过X射线衍射分析， 热应激脂质体。 将使用电子密度分布图 为了获得双层在每个施加的条件下的中等分辨率视图 渗透压 本研究选择双层膜， 两个原因第 第一，组成、结构、内聚性质， 可以精确地控制膜的静电势， 每个排斥压力的关键物理参数 调查并测试其起源的模型。 比如说 水化压力是由水化作用引起的， 层间水的电场极化。双层。 第二，膜表面之间的排斥相互作用是关键的 在许多生理过程中。 特别是，这些压力将 测定含各种糖脂或含脂质的双层 与共价连接的聚乙二醇（PEG）。 由于糖脂 被认为是介导细胞与它们的 环境下，实验设计，以确定结构和 糖脂在膜中的相互作用性质。 PEG-脂质延伸 脂质体的血液循环时间，从而允许药物递送至 实体瘤 实验旨在验证这一假设， 增加的循环时间是由于空间稳定性引起的， PEG-脂质。 提出的实验也旨在增加空间位阻。 通过改变双层基质的内聚性质来形成屏障。 将用于解决这些假设并获得 尽可能完整地描述三种界面力 包括：（1）水吸附等温线，以确定含水量 膜和水合能，（2）微量移液器操作 的单壁囊泡，以获得粘附能和内聚 膜的性质，（3）渗透应力实验作为一种 温度的函数提供了熵和熵 组分压力的贡献，（4）表面和zeta电位 测量以获得双层电场，（5）表面压力-面积 单层等温线，以获得面内相互作用之间的 PEG-脂质，和（6）差示扫描量热法，以获得相 含有PEG-脂质的双层的行为。

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.