Focal Adhesions in Cell Adhesion Strengthening

细胞粘附强化中的局部粘附

• 批准号: 6767583
• 负责人: Andres J Garcia
• 金额: $ 23.62万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6767583
• 关键词: actins; bioengineering /biomedical engineering; biological signal transduction; cell adhesion; cell adhesion molecules; cytoskeleton; extracellular matrix; focal adhesion kinase; guanine nucleotide binding protein; guanosinetriphosphatases; integrins; mathematical model; molecular biology; phosphatidylinositol 3 kinase; phosphorylation; protein signal sequence; protein structure function; tissue /cell culture

DESCRIPTION (provided by applicant): Focal adhesions are central elements of the cell adhesion process, functioning as structural links between the cytoskeleton and extracellular matrix and triggering essential signaling pathways. Because the biophysical and biochemical processes in the focal adhesion complex are tightly coupled, mechanical analyses of adhesion provide critical information on structure-function relationships for these specialzed structures. The objective of this application is to analyze the role of focal adhesion size, position, and composition in adhesion strengthening. Our central hypothesis is that focal adhesion size, position, and composition regulate adhesion strength by controlling the distribution of mechanical loading. The rationale for this research is that, once a quantitative understanding of how focal adhesions regulate adhesion strength is established, it will be possible to systematically analyze the specific roles of focal adhesion components as well as identify strategies to control adhesion. Innovative bioengineering approaches (hydrodynamic adhesion assay, micropatterned surfaces) d be integrated with unique molecular/cell biology reagents to manipulate focal adhesion assembly in order to analyze the function of these structures. Aim 1: Analyze the effects of modulating focal adhesion size and position on adhesion strength. We hypothesize that focal adhesion size and position strongly regulate adhesion strength by reinforcing adhesion clusters and distributing mechanical forces. Aim 2: Elucidate the regulatory role of focal adhesion composition in adhesion strengthening. We will test the hypothesis that focal adhesion composition is critical for regulation of adhesion strength by analyzing the role of regulatory molecules (Rho-kinase, PI %kinase, FAJS) that significantly alter focal adhesion composition. We expect this research to yield two outcomes: (i) a quantitative understanding of the regulatory role of focal adhesions in adhesion strength and (ii) a rigorous meshwork for the analysis of adhesive mechanisms and functional studies of structural and signaling components in physiological and pathological processes.

描述（由申请人提供）：粘着斑是细胞粘附过程的核心要素，充当细胞骨架和细胞外基质之间的结构连接并触发重要的信号传导途径。由于粘着斑复合物中的生物物理和生化过程紧密耦合，因此粘着斑的力学分析为这些特殊结构的结构-功能关系提供了关键信息。本应用的目的是分析粘附斑尺寸、位置和成分在粘附强化中的作用。我们的中心假设是，粘附斑的大小、位置和成分通过控制机械载荷的分布来调节粘附强度。这项研究的基本原理是，一旦对粘着斑如何调节粘连强度有了定量的了解，就可以系统地分析粘着斑成分的具体作用，并确定控制粘连的策略。创新的生物工程方法（流体动力粘附测定、微图案表面）可以与独特的分子/细胞生物学试剂相结合，以操纵粘着斑组装，从而分析这些结构的功能。目标 1：分析调节粘附斑大小和位置对粘附强度的影响。我们假设粘着斑的大小和位置通过增强粘附簇和分布机械力来强烈调节粘附强度。目标2：阐明粘着斑组合物在粘附强化中的调节作用。我们将通过分析显着改变粘着斑组成的调节分子（Rho激酶、PI%激酶、FAJS）的作用来检验粘着斑组成对于粘附强度调节至关重要的假设。我们期望这项研究产生两个成果：（i）定量了解粘着斑对粘附强度的调节作用；（ii）为分析粘附机制以及生理和病理中结构和信号成分的功能研究建立严格的网络。流程。