Ultrastructural Basis of Mechanotransduction in Matrix Adhesions

基质粘附力传导的超微结构基础

基本信息

批准号：
8550088
负责人：
DORIT HANEIN
金额：
$ 146.81万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8550088
关键词：
Accounting Actins Actomyosin Address Adhesions Affect Affinity Avidity Basal Cell Behavior Binding Binding Sites Biochemical Biochemistry Biological Biological Models Biological Process Blood Vessels Caliber Cell Adhesion Cell Culture Techniques Cell Death Cell membrane Cell physiology Cell-Matrix Junction Cells Cellular biology Chemicals Chimeric Proteins Chronic Clinical Collagen Complex Computational Science Crystal Formation Crystallization Cytoskeleton Data Defect Dependence Development Devices Dimensions Disease Dissociation Electron Microscopy Electrons Elements Embryo Endothelial Cells Environment Event Exhibits Extracellular Matrix Feedback Fibroblasts Filament Fluorescence Fluorescence Microscopy Focal Adhesions Freezing Gel Generations Goals Half-Life Heterogeneity Homeostasis Ice Image Imaging Techniques In Situ In Vitro Individual Inflammatory Integrin Binding Integrin-mediated Cell Adhesion Pathway Integrins Knowledge Lateral Learning Length Life Ligands Light Link Mechanics Mediating Membrane Methods Microscopy Modeling Modification Molecular Molecular Conformation Monitor Monomeric GTP-Binding Proteins Morphology Mus Myosin ATPase Neoplasm Metastasis Output Pathway interactions Pattern Recognition Phenotype Phosphotransferases Physiological Principal Investigator Procedures Process Property Protein Dynamics Proteins Protocols documentation Psychological reinforcement Reagent Regulation Resolution Roentgen Rays Sampling Signal Pathway Signal Transduction Spectrum Analysis Stress Fibers Stretching Structure Study models System Talin Techniques Time Variant Vinculin Water Work X ray microscopy aqueous base cell behavior cell motility cellular imaging electron tomography extracellular human BCAR1 protein in vivo insight intercellular communication light microscopy macromolecule migration millisecond nanometer neuronal cell body novel paxillin programs receptor reconstruction research study response rho sample fixation single molecule stem tomography transmission process tumor

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this Program Project is to understand in detail how integrin-mediated adhesions mature and how this process determines signaling outputs. Adhesion maturation is highly dependent on physical forces, whether from endogenous myosin or applied externally through the extracellular matrix. Thus, comparison of normal adhesion ultrastructure and dynamics with responses to applied force will elucidate mechanisms of mechanotransduction. This Program Project will develop a model for mechanotransduction at matrix adhesions that integrates adhesion ultrastructure, biochemical interactions, temporal and spatial dynamics of multiprotein assemblies and signaling networks. We will analyze mechanotransduction in the context of cell migration as an important physiological output of adhesion mechanics and signaling. To achieve this, we have formed a unique team of long-standing collaborators who will implement a multifaceted experimental approach that includes molecular cell biology, biochemistry, biophysical approaches, material science, computational and mathematical analysis, and correlated high-resolution light and electron microscopy.

描述（由申请人提供）：该计划项目的总体目标是详细了解整合素介导的粘附如何成熟以及该过程如何决定信号输出。粘附成熟高度依赖于物理力，无论是来自内源性肌球蛋白还是通过细胞外基质施加的外部力。因此，正常粘附超微结构和动力学与对施加力的响应的比较将阐明机械转导的机制。该计划项目将开发一种基质粘附力机械转导模型，该模型集成了粘附超微结构、生化相互作用、多蛋白组装的时间和空间动力学以及信号网络。我们将在细胞迁移的背景下分析机械转导，作为粘附力学和信号传导的重要生理输出。为了实现这一目标，我们组建了一个由长期合作者组成的独特团队，他们将实施多方面的实验方法，包括分子细胞生物学、生物化学、生物物理方法、材料科学、计算和数学分析以及相关的高分辨率光学和电子显微镜。