Mathematical Models for Cell Locomotion

细胞运动的数学模型

• 批准号: 9707750
• 负责人: Alexander Mogilner
• 金额: $ 11万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9707750&HistoricalAwards=false
• 关键词: Mathematical; Models; Cell; Locomotion

Mogilner 9707750 Certain kinds of cellular movements are driven by actin polymerization. The most conspicuous examples are the lamellipodia of spreading and migrating embryonic and metastatic cells. A variety of pathogenic bacteria also propel themselves by constructing behind them a polymerized tail of cross-linked actin filaments. Collective cellular movements mediated by cell-cell interactions can generate interesting spatial patterns. These patterns can shed light on intercellular communication and can be used as novel assays for understanding the molecular mechanisms of cell signaling. The goal of this research is to understand at the molecular level (i) the mechanochemical basis of force generation by polymerizing and depolymerizing actin networks, (ii) the mechanisms of spatio-angular cytoskeletal organization, (iii) patterns of collective cell motion. The investigator and his colleagues formulate a mechanochemical theory of how the thermal fluctuations of the filament tips and the membrane can be rectified by actin polymerization to generate a propulsive force. This force is controlled by soluble and transmembrane proteins that stimulate actin polymerization. The investigators also formulate a theory for retrograde flow of lamellar cytoplasm. This theory is based on two sources of contractile force: (i) the contraction of the actin gel that must accompany depolymerization, and (ii) actin filament contraction driven by myosin. The results of these models determine the relative roles of actin polymerization and myosin crosslinking and contraction during cell locomotion. These studies help forge a link between the basic biophysics of cell motility and the chemical control of cell motion. The crawling of cells over surfaces is the basis for the vitally important phenomena of phagocytosis and the migration of metastatic cells. Despite the ubiquity of cellular motions, the molecular mechanisms underlying these movements remain mysterious. The investigators undertake theoretical modeling that provides a solid quantitative basis for understanding the detailed working cycle of the cell's molecular engines. This description provides a new interdisciplinary level of understanding cell movements and new methods of predicting cell behavior in medically and technologically important situations.

莫吉尔纳9707750 某些种类的细胞运动是由肌动蛋白聚合驱动的。 最明显的例子是扩散和迁移的胚胎细胞和转移细胞的板状伪足。 许多致病细菌也通过在它们后面构建一个交联肌动蛋白丝的聚合尾巴来推动自己。 由细胞间相互作用介导的集体细胞运动可以产生有趣的空间模式。 这些模式可以揭示细胞间通讯，并可用作了解细胞信号传导的分子机制的新方法。 本研究的目标是在分子水平上理解（i）通过聚合和解聚肌动蛋白网络产生力的机械化学基础，（ii）空间角细胞骨架组织的机制，（iii）集体细胞运动的模式。 研究人员和他的同事们制定了一个机械化学理论，即如何通过肌动蛋白聚合来纠正细丝尖端和膜的热波动，以产生推进力。 这种力由刺激肌动蛋白聚合的可溶性和跨膜蛋白控制。 研究人员还提出了层状细胞质逆行流动的理论。 该理论基于收缩力的两个来源：（i）必须伴随解聚的肌动蛋白凝胶的收缩，以及（ii）肌球蛋白驱动的肌动蛋白丝收缩。 这些模型的结果确定了肌动蛋白聚合和肌球蛋白交联和收缩在细胞运动过程中的相对作用。 这些研究有助于在细胞运动的基本生物物理学和细胞运动的化学控制之间建立联系。 细胞在表面上的爬行是吞噬作用和转移细胞迁移的重要现象的基础。 尽管细胞运动无处不在，但这些运动背后的分子机制仍然是个谜。 研究人员进行理论建模，为理解细胞分子引擎的详细工作周期提供了坚实的定量基础。 这种描述提供了一个新的跨学科水平的理解细胞运动和预测细胞行为的新方法，在医学和技术上的重要情况。