STRUCTURE AND INTERACTIONS OF MODEL BIOMEMBRANES

模型生物膜的结构和相互作用

• 批准号: 2184743
• 负责人: JACOB N ISRAELACHVILI
• 金额: $ 15.61万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2184743
• 关键词: adhesions; adsorption; annexins; atomic force microscopy; biophysics; chemical hydration; electron microscopy; freeze etching; hydropathy; intermolecular interaction; light scattering; lipid bilayer membrane; membrane activity; membrane fusion; membrane model; membrane structure; molecular dynamics; molecular film; molecular rearrangement; molecular shape; phosphoglycerides; polyethylenes; pulmonary surfactants; receptor binding; scanning tunneling microscopy; thermodynamics

The forces and interactions between biological membranes are accompanied by various types of deformations and molecular rearrangements as these surfaces come into contact. Some of these interactions are non-specific (e.g., van der Waals forces) while others are very specific (e.g., ligand-receptor). Our work is aimed at gaining insights into these fundamental forces, how they depend on chemical composition, physical structures, and the molecular events accompanying deformations. These deformations depend on both the inter-membrane forces and on the intra-membrane forces (which govern properties such as elasticity, curvature, membrane compressibility, head-group area, molecular orientation, order, and fluidity). In this project, forces and interactions between model lipid and lipid-protein monolayers and bilayers will be correlated to specific structural features at the molecular level. Specific effects to be examined include charged lipid membranes, fluid-solid (biphasic) membranes, single-tailed vs double-tailed lipids, osmotically swollen bilayers, ligand-receptor interactions such as Avidin/Biotin, and the protein-lipid interactions occuring in the fusogenic protein Synexin and in the lung surfactant specific protein SP-B. A deeper understanding of the interactions between lipid and lipid- protein surfaces is of fundamental and practical importance, i.e. in the adhesion and fusion of membranes, protein-lipid interactions, cell-cell (e.g., immunological) recognition, and cell motility. These studies will also have technological applications towards understanding such processes as lubrication and nano-scale processing. Of greatest possible importance is (i) the ability to study the interactions of biological membranes and proteins in real time at the molecular level, and (ii) the development of chemicals or processes that can be used to alter the adhesion, fusion or transport of synthetic vesicles and biological cells during biotechnological processes and medical treatments. The main experimental techniques used will be (i) the Surfaces Forces Apparatus (SFA) technique for measuring the static or dynamic forces between surfaces, (ii) Freeze-fracture and in-situ frozen hydrated electron microscopy (EM) techniques to provide direct images of three-dimensional structural transitions, and (iii) Scanning Tunneling Microscopy (STM) and Atomic Force Microscopy (AFM) to resolve membrane surfaces. In addition to advances in the understanding of bilayer interactions, we will cocurrently be developing a number of experimental techniques that should also be of great value to the scientific community: 1. Development of SFA, STM and AFM into practical tools for biomaterial investigations with molecular resolution; 2. Extension of surface-forces concepts and theory into complex biological systems; 3. Development of near in vivo sample preparation techniques for SFA, TEM, STM, and AFM.

生物膜之间的力和相互作用是 伴随着各种类型的变形和分子 当这些表面接触时，重排。 其中一些 相互作用是非特异性的（例如，范德华力），而 其他非常具体（例如配体受体）。 我们的工作是 旨在获得对这些基本力量的见解，他们如何 取决于化学成分，物理结构和 伴随变形的分子事件。 这些变形 取决于膜间力和膜内部 力（控制弹性，曲率等特性， 膜可压缩性，头组面积，分子取向， 顺序和流动性）。 在这个项目中，力量和互动 在模型脂质和脂质 - 蛋白质单层和双层之间 与分子的特定结构特征相关 等级。 要检查的具体效果包括带电的脂质 膜，流体 - 固体（双相）膜，单尾vs 双尾脂质，渗透肿胀的双层，配体受体受体 抗原蛋白/生物素和蛋白质脂质等相互作用 在融合蛋白Syxin和中发生的相互作用 肺表面活性剂特异性蛋白SP-B。 对脂质和脂质之间的相互作用有更深入的了解 蛋白质表面具有基本和实际重要性，即 在膜的粘附和融合中，蛋白质脂质 相互作用，细胞细胞（例如免疫学）识别和细胞 运动。 这些研究也将具有技术应用 要理解诸如润滑和纳米级等过程 加工。 最重要的重要性是（i） 研究生物膜和蛋白质在实际中的相互作用 分子水平的时间，以及（ii）化学物质的发展 或可用于改变粘附，融合或 合成囊泡和生物细胞的运输 生物技术过程和医疗治疗。 所使用的主要实验技术将是（i）表面 用于测量静态或 表面之间的动态力，（ii）冻结和原位 冷冻水合电子显微镜（EM）技术提供 三维结构过渡的直接图像， （iii）扫描隧道显微镜（STM）和原子力 显微镜（AFM）解决膜表面。 此外 在理解双层互动方面的进步，我们将 共同开发了许多实验技术 对科学界也应该很有价值： 1。将SFA，STM和AFM开发为实用工具 分子分辨率的生物材料研究； 2。将表面概念和理论扩展到复杂 生物系统； 3。开发近近体内样品制备技术 SFA，TEM，STM和AFM。