Kinesin-Microtubule Interactions: Transport and Spindle Formation

Peter Bates (August 30, 2010)

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Microtubules are long cylindrical structures (lengths being tens of microns and diameter approximately 25 nm) comprised of tubulin dimers, which self-assemble, 13 protofilaments being required side-to-side to form the circular cross section. In the first set of results, microtubules are represented as stiff, polar rods which are subject to diffusion in position and orientation and also subject to pair-wise interaction, mediated by kinesin molecular motors. The concentration of kinesin is represented by a parameter that feeds into the probability of an interaction occurring when two microtubules collide. The probability of an interaction also depends on the location of the collision point along the lengths of the microtubules, because kinesin accumulates at the positive end of each microtubule. With collision rules in place, Monte-Carlo simulations for large numbers of freely moving microtubules are performed, adjusting parameters for concentration of kinesin and polarity of the microtubules. From these studies, a phase diagram is produced, indicating thresholds for phase change to occur. Simulation results are compared to those from in vitro experiments.

The second part of the talk involves modeling the fine scale dynamics of a kinesin motor as it walks along a microtubule. The two heads of the kinesin molecule alternately bind and unbind to the microtubule with certain mechanisms providing a directional bias to the Brownian motion expected. One bias is the shape of the head and the shape of the binding site, along with the companion electrostatic charges. The second bias is that, utilizing ATP capture and transferal of phosphors for energy, part of the polymeric leg (neck-linker) of the bound head becomes attached towards the front of that head (the lqlq zipped q q state). The trailing head detaches from the microtubule. It then becomes subject to the biased entropic force due to the zipped state of the leading head and also preferentially (because of shape orientation) attaches in front of the currently attached head at which time ADP is released and a conformational change occurs, strengthening the binding. This motion is modeled using stochastic a differential equation. Simulations are performed with different lengths of neck-linkers and the mean speeds of progression obtained. These are compared with experimental results