(347f) Microtubule Mechanics and Centrosome Positioning - the Role of Dynein

Microtubules are key components of force transmission in cells, and play a role in cell locomotion, transport, and mitosis. Experiments in Lele's group (Lele, Wu, Russell) have shown that microtubules severed by laser ablation do not straighten, as would be expected from the large bending moments along their lengths. Instead, segments near newly created minus ends typically increased in curvature following severing, while segments near new microtubule plus ends depolymerize before any observable change in shape. However, in dynein-inhibited cells, segments near the cut straightened rapidly following severing. These observations suggest that microtubules are subject to significant tangential forces, and that lateral motion of the microtubule is opposed by a large effective friction rather than  elastic forces. To help interpret the experimental results we have developed a new numerical model for intracellular microtubule mechanics, accounting for dynein-generated forces on the microtubules.

At the length scales of mammalian cells, microtubules behave as semi-flexible filaments and can be coarse-grained using the Kirchoff theory for elastic rods. We have supplemented the Kirchoff model^[1] with the stochastic growth and collapse of microtubules^[2] (the dynamic instability), and by a model for dynein generated forces^[3]. Numerical simulations of the buckling of a single microtubule can explain both the enhanced buckling at the minus end of a severed microtubule and the apparently frozen shape of the plus end. Our results suggest that microtubule shapes in vivo reflect a dynamic force balance, where bending moments are opposed by dynein-motor forces, including an effective friction from the stochastic binding and unbinding of the motors. I will present simulations of the dynamics of the centrosome, driven by the motion of ~ 100 microtubules. The results are consistent with a mechanism for centrosome centering driven by pulling forces exerted by dynein motors. I will explain how tension on the centrosome can be reconciled with buckled filaments near the cell periphery. The simulations span time scales of about 14 orders of magnitude using a projection method [4] combined with parallelization to speed up the simulations.

[1] A. J. C. Ladd and G. Misra, J. Chem. Phys. 130:124909, 2009.
[2] T. Mitchison and M. Kirschner Nature 312: 237-42, 1984.
[3] R. B. Dickinson, Private Communication, 2010.
[4] I. G. Kevrekidis, C. W. Gear and G. Hummer, AIChE J. 50:1346, 2004.