Regulation of the Micromechanical Properties of Cells by Intermediate Filaments

中间丝对细胞微机械性能的调节

• 批准号: 10227018
• 负责人: Paul A Janmey
• 金额: $ 24.58万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227018
• 关键词: 3-Dimensional; Actins; Actomyosin; Adipose tissue; Affect; Animals; Biological; Biopolymers; Blood Vessels; C-terminal; Cations; Cells; Collaborations; Cytoplasm; Cytoskeleton; Data; Diffuse; Electrostatics; Elements; Endothelium; Exhibits; Extracellular Matrix; F-Actin; Fibrosis; Filament; Frequencies; Gender; Grant; Guanosine Triphosphate Phosphohydrolases; In Vitro; Individual; Intermediate Filaments; Ions; Knock-out; Knockout Mice; Link; Liver; Measurement; Measures; Mechanical Stress; Mechanics; Mediating; Metals; Methods; Microfluidics; Microtubules; Molecular; Molecular Conformation; Movement; Mus; Optical Methods; Phosphotransferases; Polymers; Property; Regulation; Reporting; Resistance; Rheology; Role; Rupture; Side; Solubility; Stress; Structure; System; Tissues; Vimentin; Work; biophysical analysis; cell motility; crosslink; in vivo; novel; particle; polycation; polymerization; predicting response; protein crosslink; response; treatment response; viscoelasticity; water flow

Project Summary (Project 5, Janmey) Unlike other elements of the cytoskeleton, individual IFs and the networks they form can withstand large deformations that would rupture F-actin or microtubules The molecular mechanisms that control vimentin IF assembly in the cell and that link IFs together so that they form mechanically resistant networks are also not well understood. Specific crosslinking proteins do not appear to be required for network formation, and several bonds between IF subunit C-terminal extensions and the sides of other filaments have been reported. Complementary attractive interactions between vimentin IFs mediated by multivalent cations are also important. Identifying the molecular mechanisms for IF crosslinking and bundle formation remains a major challenge to defining this system with the same detail as currently available for network formation by other biopolymers. This project will define the mechanism that control vimentin polymerization and network formation in the cytoplasm, and quantify how network of purified vimentin Ifs and vimentin containing cells and cytoskeletons respond to large amplitude compressive strains that occur in vivo. The project will collaborate with other project of this PPG in both cell biologic and biophysical studies and engage the PPG animal core to produce mice and tissues with altered vimentin expression to determine the role of vimentin on tissue mechanics and responses of genetically modified mice with altered vimentin to mechanical stresses.

项目概要（项目5，Janmey） 与细胞骨架的其他元素不同，单个IF和它们形成的网络可以承受大的 变形会破坏F-肌动蛋白或微管控制波形蛋白IF的分子机制 细胞中的组装和连接IF在一起，使它们形成机械抵抗网络，也不是 很好理解。网络形成似乎不需要特定的交联蛋白， 已经报道了IF亚基C-末端延伸部分和其它丝的侧边之间的几个键。 波形蛋白IF之间由多价阳离子介导的互补吸引相互作用也是 重要.确定IF交联和束形成的分子机制仍然是一个主要的问题。 用与目前可用于其他网络形成的相同细节来定义该系统的挑战 生物聚合物本项目将明确控制波形蛋白聚合和网络的机制 在细胞质中的波形蛋白的形成，并量化纯化的波形蛋白Ifs和含有波形蛋白的细胞和 细胞骨架响应于体内发生的大幅度压缩应变。该项目将与 在细胞生物学和生物物理学研究中与PPG的其他项目合作，并使PPG动物核心参与， 产生波形蛋白表达改变的小鼠和组织，以确定波形蛋白对组织的作用 波形蛋白改变的转基因小鼠对机械应力的力学和反应。