ELECTROSTATIC POTENTIALS AND BIOLOGICAL MEMBRANES

有三个目标。第一个目标是确定 描述水扩散双层的Gouy-Chapman-Stern理论 四价阳离子，如庆大霉素，与 磷脂双层膜。结果将提供一种新的测试 基本物理理论，将对临床医生和 研究氨基糖苷类抗生素与药物相互作用的药理学家 磷脂。最近的研究表明，磷脂是“受体” 对庆大霉素的肾毒性作用负责的部位。 目的是确定膜附近的静电势 当固定费用位于德拜长度或更远 界面。膜将由两性离子的混合物形成 磷脂酰胆碱，PC和糖脂GM1，以模拟 生物膜的静电性能。GM1有一个负面影响 电荷，位于距离膜表面约1 nm处。这个 红细胞和PC：GM1囊泡的Zeta电位都约为1/3 古伊-查普曼-斯特恩理论的预测值。这些测量结果 将提供对三个新理论的第一次关键测试，这三个理论提出了 描述生物膜附近的静电势。为 这两个项目的Zeta潜势将从 对多层囊泡进行了微电泳法测量， 红细胞和VSV病毒粒子，膜内电势的变化 将通过在平面上进行的动力学电导测量来确定 在脂溶离子和载体存在的情况下的磷脂双层， 单层以上的电势的变化将被直接测量 用一个电离电极。第三个目标是测试一个新的 关于肾近端小管液体重吸收的假说。 该理论假定亥姆霍兹型电渗透使流体运动 穿过这种上皮细胞的外侧细胞间隙。这个 该项目的理论方面将与 R.马蒂亚斯博士(拉什)。这一假设将通过以下方式进行实验验证 在不同的实验条件下，测量了样品的Zeta电位。 基侧膜形成的囊泡来自于各种 上皮细胞。

There are three objectives. The first objective is to determine if the Gouy-Chapman-Stern theory of theaqueous diffuse double layer describes adequately the interaction of tetravalent cations, such as gentamicin, with phospholipid bilayer membranes. The results will provide a new test of a fundamental physical theory and will be useful to clinicians and pharmacologists studying the interaction of aminoglycoside antibiotics with phospholipids. Recent work suggests that phospholipids are the "receptor sites" responsible for the nephrotoxic effects of gentamicin. The second objective is to determine the electrostatic potential adjacent to membranes when the fixed charges are located a Debye lenght or more from the interface. Membranes will be formed from mixtures of the zwitterionic lipid phosphatidylcholine, PC, and the glycolipid GM1 to mimic the electrostatic properties of biological membranes. GM1 has one negative charge, which is located about 1 nm from the surface of the membrane. The zeta potential of both an erythrocyte and a PC:GM1 vesicle are about 1/3 the value predicted from the Gouy-Chapman-Stern theory. These measurements will provide the first critical test of three new theories that puport to describe the electrostatic potential adjacent to biological membranes. For these two projects zeta potentials will be calculated from microelectrophoresis measurements made on multilamellar vesicles, erythrocytes and VSV virions, the change in the potential within a membrane will be determined from kinetic conductance measurements made on planar phospholipid bilayers in the presence of lipid soluble ions and carriers, and the change in the potential above a monolayer will be measured directly with an ionizing electrode. The third objective is to test a new hypothesis about the reabsorption of fluid from the renal proximal tubule. The theory postulates that Helmholtz-type electro-osmosis moves fluid through the lateral intercellular spaces of this epithelium. The theoretical aspects of this project will be developed in collaboration with Dr.R. Mathias (Rush). The hypothesis will be tested experimentally by measuring, under various experimental conditions, the zeta potentials of vesicles formed from basolateral membranes isolated from a variety of epithelia.