BPS2026 – Midzone bundles of the mammalian anaphase spindle are mechanically coupled both locally and globally to coordinate chromosome segregation

To robustly segregate chromosomes, the mammalian anaphase spindle must generate and respond to force. How it does so remains poorly understood due to the difficulty of probing mechanics during anaphase’s short lifetime. Here, we use microneedle manipulation in live cells to pull on a subset of anaphase midzone bundles and ask how these force-generating units coordinate their activities in space and time to segregate the genome. We find that along the spindle’s short axis midzone bundles transmit force locally to each other with a coupling distance increasing with applied force velocity. Notably, along the spindle’s long axis midzone bundle resistance to sliding and bundle spindle anchorage are strong enough to reverse anaphase spindle elongation under applied force, in a PRC1-dependent manner. Thus, all midzone bundles must elongate for spindle elongation to occur. We propose that this strong coupling of force-generating elements across both spindle axes enables the anaphase spindle to act as a single mechanical unit that robustly coordinates the segregation of individual chromosomes yet can isolate missegregation events on longer timescales.