COMPUTATIONAL MODELS OF CELL MOTILITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 细胞迁移是生物学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，但将它们作为一个动态系统整合到细胞迁移的操作中的挑战迫在眉睫。我们正在使用虚拟单元(VC)环境来模拟运动过程。VC已经能够模拟复杂几何形状的3-D区域(细胞内部)上的反应扩散方程。因此，一个子模型的数值模拟和可视化正在开发中，该模型结合了细胞质中基本调控分子的时空动力学。这包括描述肌动蛋白单体、肌动蛋白结合蛋白和离子的化学动力学、扩散和运输的反应扩散方程。作为下一步，我们将使VC能够分别在三维域及其边界上求解细胞骨架力学和黏附系统的反应-平流-扩散方程。除了结合适当的数值基础设施来处理新的数学形式之外，一个关键的挑战将是开发生物物理学的图形表示法，用户可以部署这些图形表示法，以完全指定力学问题领域内的模型。这样的表示将按照由结构、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，以便动态地改变细胞的几何形状，以考虑细胞表面的突起/收缩运动。我们将把有限元技术应用于改变几何形状的细胞骨架动力学问题。

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.