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; 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）：焦点粘附是细胞粘附过程的中心元素，起作用充当细胞骨架和细胞外基质之间的结构联系，并触发必要的信号通路。由于焦点粘附复合物中的生物物理和生化过程是紧密耦合的，因此对这些特殊结构的结构 - 功能关系的机械分析提供了关键的信息。该应用的目的是分析焦点粘附大小，位置和组成在粘附增强中的作用。我们的中心假设是局灶性粘附大小，位置和组成通过控制机械负荷的分布来调节粘附强度。这项研究的理由是，一旦对焦点粘附如何调节粘附强度的定量了解，就可以系统地分析焦点粘附成分的特定作用，并确定控制粘附的策略。将创新的生物工程方法（流体动力粘附测定，微图案表面）与独特的分子/细胞生物学试剂集成，以操纵局灶性粘附组装，以分析这些结构的功能。目标1：分析调节焦点粘附大小和位置对粘附强度的影响。我们假设局灶性粘附大小和位置通过增强粘附簇和分配机械力来强烈调节粘附强度。目标2：阐明局灶性组成在粘附增强中的调节作用。我们将检验以下假设：焦点粘附组成对于通过分析调节分子（Rho-激酶，PI％激酶，FAJ）的作用来调节粘附强度至关重要，从而显着改变了局灶性粘附组成。我们预计这项研究将产生两个结果：（i）对焦点粘连在粘附强度中的调节作用的定量理解，以及（ii）分析粘附机制的严格网格和生理和病理过程中结构和信号成分的功能研究。