Mathematical models of cellular movements

细胞运动的数学模型

• 批准号: 0073828
• 负责人: Alexander Mogilner
• 金额: $ 16.84万
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2003-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0073828&HistoricalAwards=false
• 关键词: Mathematical; models; cellular; movements

Mogilner0073828 Three mechanisms - protrusion of the lamellipodial actinnetwork, graded adhesion of the cytoskeleton to the surface, andcytoskeletal contraction - acting in concert are both necessaryand sufficient to produce highly effective cell movement. Actualrates and forces of protrusion depend on local concentrations ofactin monomers and polymers and a host of actin capping,nucleation, polymerization and adhesion proteins near the cell'sleading edge. The investigator derives partial differentialequations that couple the chemical kinetics of all these proteinconcentrations to the model of cytoskeletal mechanics. Theseequations are solved analytically and quantify molecularmechanisms of protrusion localization at the cell's leading edgeand regulation of protrusion rates and forces. Experimentssuggest that the force of the cytoskeletal contraction is myosinpowered. The investigator models the dynamics of actin filamentsand myosin clusters in physical and angular space and describesthe actomyosin dynamic contraction mechanism quantitatively.Using this description, the investigator analyzes mechanochemicalfeedback loops between systems of traction, protrusion and gradedadhesion within the frameworks of interactive computer modelsvarying in complexity. These models are applied to migration offish keratocyte and nematode amoeboid sperm. Comparison oftheoretical results with experiment clarify the roles ofcytoskeletal, adhesion and membrane systems in cellular movementsand concepts of motility, polarizability and directionality. Themodels allow testing of plausible scenarios of cell movements. Migration of animal cells is a fundamentally importantprocess underlying the phenomena of wound healing, morphogenesisand cancer. Current experimental research is aimed at dissectingthe complex processes of migration into simpler phenomena thatcan be more easily analyzed. The investigator models thesemotility phenomena theoretically, which will allow biologists totest quantitatively the existing qualitative ideas. Specifically,the investigator examines mathematically the molecular basis andthe principles of self-organization of cell mechanics anddevelops computer models that reproduce the observed patterns ofcell locomotion. Results of the modelling will provide a newinterdisciplinary level of understanding cell movements and newmethods of predicting cell behavior in important medical andtechnological situations.

莫吉尔纳0073828 三种机制--板状伪足肌动蛋白网络的突出、细胞骨架与表面的分级粘附和细胞骨架收缩--协同作用是产生高效细胞运动的必要和充分条件。 突起的实际速率和力取决于肌动蛋白单体和聚合物的局部浓度，以及细胞前缘附近的肌动蛋白帽、成核、聚合和粘附蛋白的主体。 研究人员推导出偏微分方程，将所有这些蛋白质浓度的化学动力学耦合到细胞骨架力学模型。 这些方程的解析求解和量化的分子机制的突出定位在细胞的leading edge和调节的突出率和部队。 实验表明，细胞骨架收缩的力量是肌球蛋白提供的。 研究者在物理空间和角度空间中模拟肌动蛋白和肌球蛋白簇的动力学，定量描述肌动球蛋白的动态收缩机制，并利用这种描述，在复杂程度不同的交互式计算机模型框架内分析牵引、突出和分级粘附系统之间的机械化学反馈回路。 这些模型被应用于鱼类角膜细胞和线虫变形虫精子的迁移。 理论结果与实验的比较阐明了细胞骨架、粘附和膜系统在细胞运动中的作用以及运动性、极化性和方向性的概念。 这些模型允许测试细胞运动的合理情况。 动物细胞的迁移是伤口愈合、形态发生和癌症现象的基础。 目前的实验研究旨在将复杂的迁移过程分解为更容易分析的简单现象。 研究者从理论上模拟了这些运动现象，这将使生物学家能够定量地测试现有的定性想法。 具体地说，研究人员在数学上研究了细胞力学的分子基础和自组织原理，并开发了再现观察到的细胞运动模式的计算机模型。 建模的结果将提供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，在重要的医疗和技术情况。