Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session III Abstracts

Clusters and Comets: Regulation of Actin Assembly Leslie Loew . University of Connecticut Health Center, Farmington, CT, USA.

The dynamics of the actin cytoskeleton underlies cellular processes as migration, cytokinesis, endocytosis, and the invasion of pathogenic microbes; it also controls dynamic morphological features of cells such as dendritic spines in neurons and the foot processes of kidney podocytes. Actin polymerization is regulated in specific ways to shape these diverse functions. We have combined experiments and mathematical modeling to try to understand the upstream regulation of actin assembly. One approach has been to use the Virtual Cell modeling platform to develop comprehensive spatial models of actin dynamics. This approach has been used to understand actin dynamics at the leading edge of migrating cells triggered by nucleation promoting factors such as N-WASp. We have also used this approach to analyze how the adaptor protein, Nck recruits N-WASp and other key signaling molecules in the comet tails that propel invading microbial pathogens. But traditional modeling approaches, which track each species, cannot deal with the combinatorial complexity associated with polymerization and aggregation, both of which are key process in cytoskeletal signaling. Recently, we have begun to address the special role of molecular aggregates and clusters in cell biology. We have developed an efficient non- spatial algorithm, based on classical polymer theory developed by Flory and Stockmayer, that efficiently predicts the dynamic composition and sol-gel transition of molecular aggregates. We have also developed a novel spatial stochastic algorithm based on Langevin dynamics to accurately describe clustering of multivalent biological molecules. Both of these algorithms are being applied to signaling systems that trigger actin dynamics. (Supported by NIH grants P41GM103313 TR01DK087660 and RO1 CA82258).

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