Modeling mechanisms in cytokinesis, cell polarization and motility

项目摘要/摘要 细胞分裂、建立极化方向和爬行移动的能力需要协调 细胞骨架与膜的相互作用以及与组织的信号系统的相互作用 膜。发展预测数学和计算模型面临的一个主要挑战 亚细胞组织的这些机制是对分子间高度特异性相互作用的解释 水平导致了突发的集体行为。我们通过使用计算和 与实验者密切合作，将分子与细胞尺度联系起来的建模方法。作为我们的 模型在纳入对潜在分子机制的更准确描述方面取得了进展，他们 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)胞质分裂。我们正在模拟收缩环是如何通过凝结形成的 含有肌球蛋白和福尔马林的膜结节的宽带。我们应用粗粒度的生物物理 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 拉动肌动蛋白细丝。(2)细胞和细胞器运动。我们开发了细丝级肌动蛋白网络模型 解释了它们的树枝状网络结构、分布的周转、力的传递和机械调节 分枝和断枝。此补充请求将允许我们购买8个计算节点， 添加到利哈伊大学的HPC集群Sol/Hawk。每个节点将为我们提供450,000个核心小时数(SU) 每年总计360万个SU。

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.