COMPUTATIONAL MODELS OF CELL MOTILITY

细胞运动的计算模型

• 批准号: 7956388
• 负责人: ALEXANDER MOGILNER
• 金额: $ 8.14万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956388
• 关键词: 3-Dimensional; Accounting; Actin-Binding Protein; Actins; Adhesives; Biochemical; Biological; Biophysics; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Computer software; Cytoplasm; Diffusion; Elements; Environment; Equation; Funding; Grant; Imagery; Institution; Ions; Mechanics; Modeling; Molecular; Movement; Operative Surgical Procedures; Process; Reaction; Research; Research Infrastructure; Research Personnel; Resources; Signal Transduction; Simulate; Source; Specific qualifier value; Structure; Surface; System; Techniques; United States National Institutes of Health; cell motility; chemical kinetics; monomer; simulation; virtual

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它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不断被识别，但将它们作为动力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 已经能够在复杂几何形状的 3D 域（细胞内部）上模拟反应扩散方程。因此，正在开发子模型的数值模拟和可视化，其中结合了细胞质中重要调节分子的时空动力学。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。下一步，我们将使用 VC 分别求解 3D 域及其边界上的细胞骨架力学和粘附系统的反应-平流-扩散方程。除了整合适当的数字基础设施来处理新的数学形式之外，一个关键的挑战是开发生物物理学的图形表示，用户可以部署该图形表示，以在支持力学的问题域中完全指定模型。这种表示将根据易于操作的组件集来构建，这些组件由结构、分子和相关相互作用组成。最后，我们将扩展 VC 软件，以便动态改变细胞几何形状，以解释细胞表面的突出/缩回运动。我们将采用有限元技术来解决几何形状变化的细胞骨架动力学问题。