STRUCTURE AND INTERACTIONS OF MODEL BIOMEMBRANES III

模型生物膜 III 的结构和相互作用

• 批准号: 6042713
• 负责人: JACOB N ISRAELACHVILI
• 金额: $ 24.11万
• 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 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6042713
• 关键词: artificial membranes; atomic force microscopy; bioengineering /biomedical engineering; biomaterial compatibility; biomaterial development /preparation; biomimetics; drug delivery systems; electron microscopy; fluorescence microscopy; intermolecular interaction; lipid bilayer membrane; mathematical model; membrane activity; membrane model; membrane proteins; membrane structure; molecular dynamics; molecular rearrangement; nanotechnology; protein protein interaction; scanning tunneling microscopy; selectins

We hypothesize that "softly supported" bilayers incorporating selectins are excellent in vitro models for Surface Force Apparatus (SFA) measurements of the 'rolling forces' between complementary surfaces expressing selectins and its ligands. Isolating the molecular features (static and dynamic forces, mobility, on and off rates, etc.) of the specific ligands and receptors that control cell-cell and cell-substrate adhesion is difficult in vivo, although necessary for determining the basic rules governing cell sorting, tissue differentiation, pathological deformations and growths, and the body's control of cell population size and location. In addition, the dynamics of specific adhesion, i.e., of receptor -ligand pairs, is essential for understanding the body's immune response and in the biomimetic construction of drug delivery systems. The specific systems to be examined include: (1) Measurement and characterization of biomolecular and biosurface interactions. The Surface Forces Apparatus (SFA), AFM, and optical microscopy will be employed to measure bilayer, membrane and specific protein (e.g., ligand-receptor) interactions of softly-supported bilayers and monolayers. Specific systems will include: (1) the dynamic interactions of P-selectin proteins with various ligands such as lipid bilayers exposing polysaccharide headgroups (selectins are an important family of adhesion and recognition proteins), (2) DNA-lipid biolayer interactions which are primarily important for DNA transfection agents such as DNA- encapsulating vesicle delivery systems; (3) comparing these interactions to PEG-tethered biotin-lipids and streptavidin, this being a genetic tethered system with strong ligand-receptor bonds of varying tether length. (2) Biomimetic construction of complex structures. We plan to determine optimal methods of initiating, limiting, and controlling vesicle aggregation to produce aggregates of defined size and composition by manipulating (i) ligand-receptor stoichiometry, (ii) ligand-receptor "on- rates" through control of electrostatic or steric repulsions induced by pH, divalent ions and (iii) bilayer-bilayer and vesicle-vesicle interactions through control of surface charge or polymeric steric layers, ionic strength, or divalent ions. We also will study metastable bilayer structures for use as generic encapsulating membranes. The systems will include (i) mixtures of saturated phospholipids, cholesterol and polymer lipid that form open discs, and (ii) mixtures of long and short chain phosphatidylcholines, that form bilayer discs at low temperatures but close to form vesicles at higher temperatures, and (iii) ethanol interdigitated bilayers of DPPC that also form temperature dependent discs.

我们假设，掺入Selectins的“软支持”的双层是表面力设备（SFA）测量的极好的体外模型，以表达Selectins及其配体的互补表面之间的“滚动力”测量。在体内很难隔离特定的配体和受体的分子特征（静态和动态力，迁移率，开关和关闭速率等）在体内难以控制细胞细胞和细胞 - 覆盖的受体，尽管对于确定细胞分类的基本规则，组织差异，病理不适，病理错误和生长以及细胞的体积和位置的控制是必不可少的。此外，特定粘附的动力学，即受体 - 配对对，对于理解人体的免疫反应和药物输送系统的仿生结构至关重要。要检查的特定系统包括：（1）生物分子和生物表面相互作用的测量和表征。将采用表面力设备（SFA），AFM和光学显微镜来测量双层，膜和特异性蛋白（例如配体受体受体）的相互作用，以柔软支持的双层和单层。 Specific systems will include: (1) the dynamic interactions of P-selectin proteins with various ligands such as lipid bilayers exposing polysaccharide headgroups (selectins are an important family of adhesion and recognition proteins), (2) DNA-lipid biolayer interactions which are primarily important for DNA transfection agents such as DNA- encapsulating vesicle delivery systems; （3）将这些相互作用与钉蛋白生物素 - 脂质和链霉亲和素进行比较，这是一个遗传束缚的系统，具有较强的绑带长度的配体 - 受体键。 （2）复杂结构的仿生结构。我们计划确定最佳的启动，限制和控制囊泡聚集的方法，以通过操纵（i）配体 - 受体镇静剂计量来产生定义的尺寸和组成骨料，（ii）配体 - 受体受体“通过pH，divers and divalent and（III II II II II II）诱导的ph，III II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II型骨骼。通过控制表面电荷或聚合物空间层，离子强度或二价离子。我们还将研究亚稳态结构，以用作通用封装膜。 The systems will include (i) mixtures of saturated phospholipids, cholesterol and polymer lipid that form open discs, and (ii) mixtures of long and short chain phosphatidylcholines, that form bilayer discs at low temperatures but close to form vesicles at higher temperatures, and (iii) ethanol interdigitated bilayers of DPPC that also form temperature dependent discs.