COMPUTATIONAL MODELS OF CELL MOTILITY

细胞运动的计算模型

• 批准号: 7366493
• 负责人: ALEXANDER MOGILNER
• 金额: $ 5.11万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7366493
• 关键词: COMPUTATIONAL; MODELS; CELL; MOTILITY

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cell migration is a superb example of biological complexity, as it intertwines biochemical signaling networks with biophysical locomotory processes. While the myriad of molecular components and interactions continue to become identified, the challenge looms to integrate them all into the operation of cell migration as a dynamical system. We are using the Virtual Cell (VC) environment to enable simulations of the locomotory process. The VC is already able to simulate reaction-diffusion equations on the 3-D domains (cellular interior) of complex geometries. Thus, numerical simulation and visualization of a sub-model are being developed that incorporate spatio-temporal dynamics of essential regulatory molecules in the cytoplasm. This includes reaction-diffusion equations describing chemical kinetics, diffusion and transport of actin monomers, actin binding proteins and ions.. As the next step, we are enabling VC to solve the reaction-advection-diffusion equations of cytoskeletal mechanics and adhesive system on the 3-D domains and their boundaries, respectively. In addition to incorporating the appropriate numerics infrastructure to deal with the new mathematical formalisms, a key challenge will be to develop graphical representations of the biophysics that can be deployed by the user to fully specify models within a mechanics-enabled problem domain. Such representations would be structured in terms of easily manipulatable sets of components consisting of the structures, molecules, and relevant interactions. Finally, we will expand the VC software in order to dynamically change the cellular geometry to account for the protrusion/retraction movements of the cellular surface. We will adapt finite element techniques to problems of cytoskeletal dynamics with changing geometries.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。细胞迁移是生物复杂性的一个极好的例子，因为它将生化信号网络与生物物理运动过程交织在一起。虽然无数的分子成分和相互作用继续被识别，但挑战在于将它们作为一个动力系统整合到细胞迁移的操作中。我们正在使用虚拟细胞（VC）环境来模拟运动过程。VC已经能够在复杂几何形状的三维域（细胞内部）上模拟反应扩散方程。因此，正在开发一个子模型的数值模拟和可视化，其中包含细胞质中基本调节分子的时空动态。这包括描述化学动力学的反应扩散方程，肌动蛋白单体的扩散和运输，肌动蛋白结合蛋白和离子。下一步，我们将使VC分别在三维结构域及其边界上求解细胞骨架力学和粘附系统的反应-平流-扩散方程。除了结合适当的数字基础设施来处理新的数学形式化之外，一个关键的挑战将是开发生物物理学的图形表示，可以由用户部署，以在启用力学的问题域内完全指定模型。这种表示将根据由结构、分子和相关相互作用组成的易于操作的组件集来构建。最后，我们将扩展VC软件，以便动态改变细胞几何形状，以考虑细胞表面的突出/收缩运动。我们将采用有限元技术来解决几何形状变化的细胞骨架动力学问题。