Microscopic modeling of mitotic spindle reveals the function of its chiral shape

The mitotic spindle is a complex micro-machine built from microtubules and associated proteins, with a purpose to properly separate genetic material into two nascent cells. In our previous work we found that microtubule bundles in human spindles follow a left-handed helical path [1], from which we concluded that torques, in addition to forces, exist in the mitotic spindle. However, the microscopic explanation of torques in the mitotic spindle is still missing. To address this question, we have developed a model that represents microtubules as flexible rods, which are cross-linked by motor proteins and passive linkers. By solving the model, we found that single-molecule rotational forces regulate the volume of mitotic spindle, where larger twisting moment increases the spindle width. The model predicts the angular distribution of microtubules at the pole, based on experimentally observed shapes of microtubule bundles in the spindle midzone. This prediction is in the agreement with the current status of EM microscopy [2]. In conclusion, our theoretical description of the entire spindle elucidates both the function of twisting torque in the mitotic spindle, as well as its interplay with the anchorage of microtubules at the spindle poles.

[1] Novak, M., Polak, B., Simunic, J. et al. The mitotic spindle is chiral due to torques within microtubule bundles. Nat Commun 9, 3571 (2018).

[2] Kiewisz, R., Fabig, G., Conway, W., Baum, D., Needleman, D., Müller-Reichert, T. Three-dimensional structure of kinetochore-fibers in human mitotic spindles. eLife 11:e75459 (2022)