PBIO SEMINAR SERIES

Computer simulation as a tool for exploring cytoskeletal dynamics.

Wednesday - March 28, 2007
06-07 Seminar Series

Garry Odell
Director, Center for Cell Dynamics, Professor of Biology Friday Harbor Laboratory, University of Washington
Speaker's website

Host: Chip Asbury

I will discuss a computer simulation model that demonstrates how simple mechanochemical interactions among myriad cytoskeletal parts can yield emergent dynamics that animate cells. These mechanistic, realistic models involve numerical solution of hundreds of thousands differential equations to resolve newtonian force balance laws characterizing the individual cytoskeletal parts, undergoing brownian motion, wandering freely in 3-D space, and interacting with anything they bump into by exchanging appropriate forces. I'll present three applications of this model. The first involves pronuclear fusion and centration in C. elegans (nematode worm) embryos in which microtubules grow, from centrosomes attached initially to the male pronucleus, throughout the cell's cytoplasm. Many dynein molecular motor proteins can attach to the cell cortex and to nuclear membranes, and exert force to walk along these microtubules toward the centrosomes. The emergent consequence is to pull the male and female pronuclei, which start at opposite ends of the egg cell, together and then center them in the cell. When we experimentally knock out dyneins in real embryos, pronuclear fusion and centration 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 dynein/dynactin motors plus the effects of CLIP170 on microtubule catastrophe rates. Of more general biological interest is using the computer model to explore a mechanism I propose for regulating the lengths of dynamically unstable microtubules so that, on average, they stop elongating when they encounter the cell cortex. Finally, and of most interest biologically, I use this model to quantify the consequences of an hypothesis Victoria Foe is proposing for how and why kinesins can deliver cargo all the way to the cortex much more effectively along stable microtubules than along dynamically unstable microtubules. Foe discovered that, in anaphase in echinoderm embryos, a subpopulation of stable microtubules arises and these point toward, and make contact with, the future cytokinetic furrow zone. We believe that kinesins deliving a rho-activating cargo preferentially along these stable microtubules (after which activated rho activates cytoplasmic myosin II) is the long-sought explanation for how the microtubules of the mitotic apparatus determines the location of the contractile ring. The computer model shows that this hypothesis works/fails depending on a few details of the kinesins' behavior.