COMPUTATIONAL MODELS OF CELL MOTILITY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞迁移是生物复杂性的一个极好的例子，因为它将生物化学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，但挑战迫在眉睫，将它们全部整合到细胞迁移的操作中作为一个动力系统。我们正在使用虚拟单元（VC）环境来模拟运动过程。VC已经能够在复杂几何形状的3-D域（细胞内部）上模拟反应扩散方程。因此，数值模拟和可视化的子模型正在开发中，将时空动态的细胞质中的重要调控分子。这包括描述化学动力学、肌动蛋白单体、肌动蛋白结合蛋白和离子的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3-D域及其边界上求解细胞骨架力学和粘附系统的反应-对流-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主义，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，以充分指定模型内的力学启用的问题域。这样的表示将根据由结构、分子和相关相互作用组成的易于操纵的组件集合来构造。最后，我们将扩展VC软件，以便动态地改变细胞的几何形状，以解释细胞表面的突出/缩回运动。我们将采用有限元素技术来解决细胞骨架动态变化的几何问题。

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.