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: 6272726
• 负责人: DIMITRIJE STAMENOVIC
• 金额: $ 26.31万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6272726
• 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 器官在许多方面起作用。然而，人们对此知之甚少 控制细胞力学的基本生物物理机制， 尤其是它抵抗形状变形的能力。目标是 本项目的主要目的是了解 电池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，被组织成一个离散的(与连续的相对)， 相互关联的预应力结构。出现的具体预测 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预应力增大而增大 并随着外加剪力的增加近似线性地增加 压力。体内的关键分子成分和特定机制 解释细胞的这些机械特性的细胞骨架 将会被确认。该假说预测微丝 在提供预应力方面发挥主要作用。这些机制将是 用药理学方法调节的：手段。这一假说预言 支气管收缩会增加细胞骨架的张力， 因此，增加预应力，从而产生剪力 僵硬。将开发一个理论框架，以更好地 了解电池的机械性能及其 与潜在的细胞微结构之间的关系。钥匙 在这个项目中将使用的探头是磁扭转 细胞学。虽然这里讨论的机制可能适用于附着者 所有类型的细胞，这个项目将主要关注，但不是 对人体呼吸道平滑肌细胞的作用，因为它的 与肺功能的许多方面有关。