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Mitosis is a fundamental process that ensures each daughter cell inherits an exact copy of the genetic material. Failures in this process can lead to developmental disorders and cancer. To divide accurately, cells must compact their DNA into chromosomes and align them precisely using the mitotic spindle, a dynamic bipolar structure. Its function relies on a finely balanced network of forces generated by molecular motors, non-motor proteins, and the intrinsic dynamics of microtubules. Yet, how these diverse activities are integrated to assemble a functional spindle and ensure accurate chromosome segregation remains poorly understood.
Our recent work has revealed a unique force-generating system at growing microtubule tips. Here, microtubule tip-tracking proteins cooperate with minus-end–directed motors to produce both pushing and pulling forces on interpolar microtubules. Unlike force generators within spindle overlaps, this system harnesses polymerisation-driven forces at microtubule ends. Such tip-based forces are sufficient to establish and maintain bipolar spindle organisation in cells, offering new perspectives on how mechanical forces fine-tune spindle size and architecture. These findings uncover a distinct and scalable contribution to spindle mechanics, broadening our understanding of how spindle architecture is maintained.
An important emerging question is how spindle-derived forces are coupled to chromosome properties. Recent discoveries suggest that microtubule motors such as chromokinesins may also remodel chromosome organisation at the spindle interface. I will also briefly discuss future directions aimed at uncovering how these motors integrate mechanical activity with chromosome organisation to ensure faithful chromosome segregation. Together, these insights highlight how the interplay between microtubule-generated forces and chromosome organisation underpins faithful chromosome segregation, offering new perspectives on the origins of chromosome instability during cell division.