Most essential mammalian cell functions, including migration and cell division, involve force generation by semi-flexible biopolymers called microtubules. 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. In conjunction with experimental and modeling groups led by Profs. Tanmay Lele and Richard Dickinson we are carrying out numerical simulations of microtubules under the action of dynein motor forces to help interpret optical microscopy experiments tracking the motion of microtubules in living cells. Numerical simulations of centrosome centering and an interpretation of the experiments can be found here.
Despite their rigidity, microtubules in living cells bend significantly during polymerization resulting in greater curvature than can be explained by thermal forces alone. However, the source of the non-thermal forces that bend growing microtubules remains obscure. We have analyzed the motion of microtubule tips in NIH-3T3 fibroblasts expressing EGFP-EB1, a fluorescent +TIP protein that specifically binds to the growing ends of microtubules. We found that dynein inhibition significantly reduced the deviation of the growing tip from its initial trajectory. Inhibiting myosin modestly reduced tip fluctuations, while simultaneous myosin and dynein inhibition caused no further decrease in fluctuations compared to dynein inhibition alone. Our results can be interpreted with a model in which dynein linkages play a key role in generating and transmitting fluctuating forces that bend growing microtubules.