The mitotic spindle is chiral due to torques within microtubule bundles

• Published in: Nature communications Vol. 9; no. 1; pp. 3571 - 10
• Main Authors: Novak, Maja, Polak, Bruno, Simunić, Juraj, Boban, Zvonimir, Kuzmić, Barbara, Thomae, Andreas W., Tolić, Iva M., Pavin, Nenad
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-09-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 14/1; 14/19; 14/34; 14/35; 14/63; 631/57/2266; 631/80/128/1653; 631/80/641/1656; Anaphase; Bundles; Bundling; Cell Line, Tumor; Chirality; Chromosomes; Deactivation; Handedness; HeLa Cells; Humanities and Social Sciences; Humans; Inactivation; Kinesin; Kinesins - genetics; Kinetochores - physiology; Kinetochores - ultrastructure; Metaphase; Microscopy, Confocal; Microtubules; Microtubules - physiology; Microtubules - ultrastructure; Mitosis; Models, Theoretical; multidisciplinary; Proteins; Science; Science (multidisciplinary); Spindle Apparatus - genetics; Spindle Apparatus - physiology; Spindle Apparatus - ultrastructure; Spindles; Torque; Twisting
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06005-7

Mitosis relies on forces generated in the spindle, a micro-machine composed of microtubules and associated proteins. Forces are required for the congression of chromosomes to the metaphase plate and their separation in anaphase. However, besides forces, torques may exist in the spindle, yet they have not been investigated. Here we show that the spindle is chiral. Chirality is evident from the finding that microtubule bundles in human spindles follow a left-handed helical path, which cannot be explained by forces but rather by torques. Kinesin-5 (Kif11/Eg5) inactivation abolishes spindle chirality. Our theoretical model predicts that bending and twisting moments may generate curved shapes of bundles. We found that bundles turn by about −2 deg µm
−1
around the spindle axis, which we explain by a twisting moment of roughly −10 pNµm. We conclude that torques, in addition to forces, exist in the spindle and determine its chiral architecture.
Forces are required for congression of chromosomes by microtubule spindles. Here, using super-resolution microscopy and computational modelling, the authors find that in addition to forces, torques caused by the microtubule motor protein kinesin-5 induce chirality and curves into the spindle.