Modeling mechanisms in cytokinesis, cell polarization and motility

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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.