RESISTANCE OF THE CELL TO SHAPE DISTORTION--BASIS OF CYTOSKELETAL MECHANICS

细胞对形状变形的抵抗力--细胞骨架力学基础

• 批准号: 6109756
• 负责人: DIMITRIJE STAMENOVIC
• 金额: $ 27.43万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6109756
• 关键词: acrylamides; biological signal transduction; bradykinin; cell biology; cytochalasins; cytoskeleton; elasticity; extracellular matrix; histamine; ligands; lung; mathematical model; mechanical pressure; mechanical stress; microfilaments; microtubules; polymers; respiratory pharmacology; tissue /cell culture

Mechanical forces acting on cells, or generated by cells, influence organ functions in many ways. Little is known, however, about the basic biophysical mechanisms that govern mechanics of the cell and, in particular, its ability to resist distortion of shape. The goal of this Project is to understand the relationship between the structure of the cell and its ability to resist distortion of shape. In this project, the central hypothesis Is that the resistance of the cell to shape distortion is provided by the cytoskeleton, organized as a discrete (as opposed to continuum), interconnected, prestressed structure. Specific predictions arising from this hypothesis will be tested, most notably that the cytoskeletal shear stiffness increases with increasing prestress and increases approximately linearly with increasing applied shear stress. Key molecular components and specific mechanism within the cytoskeleton that account for these mechanical properties of cells will be identified. The hypothesis predicts that microfilaments play a major role in providing prestress. These mechanisms will be modulated using pharmacological:means. The hypothesis predicts that bronchoconstrictors will increase cytoskeletal tension and, therefore, increase the prestress and as a result the shear stiffness. A theoretical framework will be developed to better understand the mechanical properties of the cell and their relationship to the underlying cellular microstructure. The key probe that will be utilized in this project is magnetic twisting cytometry. While the mechanism addressed here may apply to adherent cells of all kinds, this project will focus mostly, but not exclusively, on the human airway smooth muscle cell because of its relevance to many aspects of lung functions.

作用于细胞或由细胞产生的机械力影响 器官的功能有很多种然而，人们对它知之甚少。 控制细胞力学的基本生物物理机制， 特别是其抵抗形状变形能力。目标 本项目的目的是了解 细胞的结构及其抵抗变形的能力 形状在这个项目中，中心假设是， 电池对形状变形的抵抗力由 细胞骨架，组织为离散的（与连续体相反）， 相互连接的预应力结构具体预测 这一假设将得到检验，最值得注意的是， 细胞骨架剪切刚度随着预应力的增加而增加 并且随着所施加的剪切力的增加而近似线性地增加 应力关键的分子组成和特定的机制， 解释细胞机械特性的细胞骨架 将被识别。该假说预测， 在提供预应力方面起主要作用。这些机制将 使用药理学调节：手段。该假说预测， 支气管收缩剂将增加细胞骨架张力， 因此，增加预应力， 刚度将建立一个理论框架， 了解细胞的机械特性及其 与底层细胞微结构的关系。关键 将在本项目中使用的探头是磁扭曲 细胞仪虽然这里所述的机制可以适用于粘附性， 细胞的所有种类，这个项目将主要集中，但不是 仅对人气道平滑肌细胞，因为其 与肺功能的许多方面相关。