Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size

• Published in: Nature communications 2024-11, Vol.15 (1), p.9865-16, Article 9865
• Main Authors: Chu, Lee-Ya, Stedman, Daniel, Gannon, Julian, Cox, Susan, Pobegalov, Georgii, Molodtsov, Maxim I.
• Format: Article
• Language: English
• Subjects: 101/62; 132/124; 14/19; 14/34; 14/35; 14/63; 631/57; 631/80/128/1653; 631/80/641/1656; 82/1; 82/80; 82/83; Animals; Biomechanical Phenomena; Cell division; Cell size; Chromosome Segregation; Chromosomes; Harnesses; Humanities and Social Sciences; Humans; Kinesins - genetics; Kinesins - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules; Microtubules - metabolism; Mitosis; Molecular motors; Motor task performance; multidisciplinary; Proteins; Pushing; Science; Science (multidisciplinary); Spindle Apparatus - metabolism; Spindles; Tips
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-54123-2

Correct mitotic spindle size is required for accurate chromosome segregation during cell division. It is controlled by mechanical forces generated by molecular motors and non-motor proteins acting on spindle microtubules. However, how forces generated by individual proteins enable bipolar spindle organization is not well understood. Here, we develop tools to measure contributions of individual molecules to this force balance. We show that microtubule plus-end binding proteins act at microtubule tips synergistically with minus-end directed motors to produce a system that can generate both pushing and pulling forces. To generate pushing force, the system harnesses forces generated by the growing tips of microtubules providing unique contribution to the force balance distinct from all other motors that act in the mitotic spindle. Our results reveal that microtubules are essential force generators for establishing spindle size and pave the way for understanding how mechanical forces can be fine-tuned to control the fidelity of chromosome segregation. Forces that lead to stable bipolar organization of mitotic spindles are poorly understood. Here the authors show that growing interpolar microtubules make a unique contribution to the overall force balance, distinct from all other motors in the spindle.