Modeling mechanisms in cytokinesis, cell polarization and motility

胞质分裂、细胞极化和运动的建模机制

• 批准号: 10805161
• 负责人: Dimitrios Vavylonis
• 金额: $ 8.63万
• 依托单位: LEHIGH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10805161
• 关键词: Accounting; Actins; Address; Basic Science; Behavior; Binding; Cell physiology; Cells; Collaborations; Computer Models; Cytokinesis; Cytoskeleton; Development; Filament; Future; Grain; High Performance Computing; Hour; Lead; Link; Mechanics; Medical Research; Membrane; Methods; Microfilaments; Modeling; Molecular; Motion; Myosin ATPase; Neoplasm Metastasis; Neurons; Organelles; Organism; Physical condensation; Regulation; Shapes; Signal Transduction; Structure; System; Universities; biophysical model; cancer cell; cell motility; cluster computing; computing resources; experimental study; mathematical model; network models; polarized cell; transmission process

Project Summary/Abstract The ability of cells to divide, establish a polarization direction, and move by crawling requires the coordinated interactions of the cytoskeleton with membranes as well as with the signaling system organizing on membranes. A major challenge for the development of predictive mathematical and computational models of these mechanisms of subcellular organization is accounting of how highly specific interactions at the molecular level lead to the emergent collective behavior. We address this complexity by employing computational and modeling methods linking molecular to cellular scales, in close collaboration with experimentalists. As our models progress to incorporate more accurate descriptions of the underlying molecular mechanisms, they require use of High-Performance Computing (HPC) resources. In particular, two of our projects are entirely dependent on HPC. (1) Cytokinesis. We are modeling how the contractile ring forms through the condensation a broad band of membrane-bound nodes containing myosin and formin. We apply coarse-grained biophysical modeling to understand the ultrastructure of nodes and how this organization impacts their ability to capture and pull actin filaments. (2) Cell and organelle motility. We develop filament-level actin network models that account for their dendritic network structure, distributed turnover, force transmission and mechanical regulation of branching and severing. This supplement request will allow us to purchase 8 computing nodes that will be added to Lehigh University's HPC cluster Sol/Hawk. Each node will provide us with 450,000 core hours (SUs) per year for a total of 3.6 million SUs per year.

项目概要/摘要 细胞分裂、建立极化方向和爬行移动的能力需要协调 细胞骨架与膜以及信号系统的相互作用 膜。预测数学和计算模型发展的主要挑战 亚细胞组织的这些机制正在解释分子间相互作用的高度特异性 水平导致集体行为的出现。我们通过采用计算和 与实验学家密切合作，将分子尺度与细胞尺度联系起来的建模方法。作为我们的 模型不断进步，能够更准确地描述潜在的分子机制，它们 需要使用高性能计算 (HPC) 资源。特别是，我们的两个项目完全是 依赖于 HPC。 (1)细胞分裂作用。我们正在模拟收缩环如何通过凝结形成 含有肌球蛋白和福尔明的宽膜结合节点。我们应用粗粒度生物物理学 建模以了解节点的超微结构以及该组织如何影响其捕获能力 并拉动肌动蛋白丝。 (2)细胞和细胞器的运动。我们开发了丝级肌动蛋白网络模型 解释它们的树突网络结构、分布式周转、力传递和机械调节 的分枝和切断。该补充请求将允许我们购买 8 个计算节点，这些节点将用于 添加到 Lehigh 大学的 HPC 集群 Sol/Hawk。每个节点将为我们提供450,000个核心小时（SU） 每年总计 360 万个 SU。