Computer Simulation as a Tool for Exploring Cytoskeletal Dynamics

Garrett Odell

Center for Cell Dynamics, University of Washington

I will discuss a computer simulation model that demonstrates how simple mechanochemical interactions among the myriad protein parts of phylogenetically universal cytoskeletal genetic networks can yield emergent dynamics that animates cells. These realistic models involve numerical solution of tens to hundreds of thousands differential equations to resolve newtonian force balance laws as tens of thousands of individual cytoskeletal parts, undergoing brownian motion in 3-D space, wander freely and interact with anything they bump into by exchanging appropriate forces. These are large computations run on a linux cluster. One example models the phenomenon of pronuclear fusion and centration in C. elegans embryos. In experiments, knocking out cytoplasmic dynein/dynactin causes these phenomena to fail. I am therefore attempting an in silico reconstitution of these phenomena involving a minimal parts list: nuclei, centrosomes, microtubules, the cell's cortex, and a single molecular motor: dynein/dynactin plus the effects of CLIP170 on microtubule catastrophe rates. Computer-animated movies show the lifelike behavior that emerges from the molecular interactions, and these turn out, mysteriously, to include realistic pronuclear fusion, rotation, and centration. Of more general biological interest is using this model to explore a CLIP170-related mechanism by which collision with a cell's cortex might induce catastrophes that cause polymerizing microtubule tips to depolymerize instead.

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