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Effects of dynein on microtubule mechanics and centrosome positioning

Tanmay Lele (University of Florida), Richard Dickinson (University of Florida), Anthony Ladd (), Jun Wu (), Gaurav Misra ()

Mechanics and Physics of Biological Cells

Wed 10:45 - 12:15

Barus-Holley 141

Microtubules have a thermal persistence length of several millimeters but in living cells they are frequently observed to be bent on length scales of just a few microns, indicating the action of large athermal forces. Most experimental force measurements with microtubules have been performed in vitro and are not directly relevant to what happens in vivo. As a result, the microtubule force balance remains unclear. To determine forces on intracellular microtubules, we measured shape changes of individual microtubules following laser severing in living cells. Regions near newly created minus ends increased in curvature following severing, whereas regions near new microtubule plus ends depolymerized without any observable change in shape. With dynein inhibited, regions near severed minus ends straightened rapidly following severing. These observations suggest that dynein exerts a pulling force on the microtubule that buckles the newly created minus end. Moreover, the lack of any observable straightening suggests that dynein prevents lateral motion of microtubules. To explain these results, we developed a model for intracellular microtubule mechanics that predicts the enhanced buckling at the minus end of a severed microtubule. Our results show that microtubule shapes reflect a dynamic force balance in which dynein motor and friction forces dominate elastic forces arising from bending moments. A centrosomal array of microtubules subjected to dynein pulling forces and resisted by dynein friction is predicted to center on the experimentally observed time scale, with or without the pushing forces derived from microtubule buckling at the cell periphery.