BIOPHYSICAL MODELS OF CELL MOTILITY

细胞运动的生物物理模型

• 批准号: 3130891
• 负责人: MICAH DEMBO
• 金额: $ 17.96万
• 依托单位: UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3130891
• 关键词: actins; alpha actinin; biophysics; cell cycle; cell motility; cinemicrography; computer graphics /printing; cytoskeleton; fluidity; gel; intracellular; mathematical model; microfilaments; microtubules; myosins; phagocytosis; phase change; physical model; polymerization; videotape /videodisc; viscosity

The actin filamant system of eukaryotic cells is the dynamical structure primarily responsible for the so called "amoeboid" motions: phagocytosis, cytokinesis, pseudopodal extension/retraction, cytoplasmic streaming, cell spreading and crawling locomotion on surfaces. The advent of supercomputers and the associated technology for numerically solving systems of nonlinear partial differential equations makes it possible to investigate the properties of realistic continuum mechanical models of the actin filament system. This means that, for the first time, the detailed comparison of theories of cell motion with the results of observation and experiment can be carried through. The potential impact of continuum mechanics and supercomputers on biological understanding of the cytoskeleton and amoeboid motility can be gauged by reference to the revolutionary changes currently underway in the area of macro-molecular structure and function. To realize these potentialities, however, existing theoretical work must be greatly extended. In the past, computational methods for solving models of the cytoplasmic mechanics have been restricted to the confined motions of isotropic contractile networks (i.e., motions within a fixed spatial domain in which the actin filaments are randomly orientated). As a results, these methods could not be applied to many of the most interesting forms of cell motility (e.g., pseudopodal extension). It is now proposed to improve existing continuum models and associated numerical techniques so as to remove these limitations. We propose to demonstrate the practical utility of our theoretical and computational methodologies by carrying out detailed mechanical analyses of experimental systems for which good data are available. The first such analysis will be of the problem of the stability and self assembly of the monopodial form and the connected problem of pseudopodial extension in the giant free living amoebae such as A. proteus. Subsequently, we propose to analyze the dynamics of the leading lamella of tissue culture cells such as fibroblasts.

真核细胞的肌动蛋白调控系统是一种动态结构， 主要负责所谓的“变形”运动：吞噬作用， 胞质分裂，伪足伸展/收缩，细胞质流动， 细胞在表面上的伸展和爬行运动。的出现 超级计算机及其相关的数值求解技术 非线性偏微分方程组使得 研究现实的连续力学模型的性质， 肌动蛋白丝系统。这意味着，首次， 细胞运动理论与 可以进行观察和实验。的潜在影响 连续介质力学和超级计算机对生物学的理解 细胞骨架和变形虫的运动性可以通过参考 目前在大分子领域正在发生的革命性变化 结构和功能。然而，为了实现这些潜力， 现有的理论工作必须大大扩展。在过去， 细胞质力学模型的计算方法 一直局限于各向同性收缩的局限运动， 网络（即，在一个固定的空间域内的运动， 细丝是随机取向的）。因此，这些方法不能 应用于许多最有趣的细胞运动形式（例如， 伪足伸展）。现在建议改善现有的连续性， 模型和相关的数值技术，以消除这些 局限性。我们建议证明我们的实际效用， 理论和计算方法进行详细的 实验系统的力学分析， available.第一个这样的分析将是对问题的 单轴形式和连接形式的稳定性和自组装 在巨大的自由生活的变形虫中伪足延伸的问题， 为.变形杆菌。随后，我们建议分析的动态 组织培养细胞如成纤维细胞的主导层。