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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).
