Coordinated chromosome motion emerges from mechanical coupling mediated by the physical spindle environment

Abstract During metaphase, chromosomes undergo oscillatory motion and exhibit distance-dependent coordinated movement with neighboring chromosomes within the spindle. However, the physical mechanism that gives rise to coordinated chromosome motion remains unclear. Here, we combine quantitative live-cell imaging in PTK1 cells, targeted perturbations of spindle microtubules and chromatin, and minimal mechanical modeling to uncover the mechanical basis of chromosome coordination during metaphase. We show that chromosome oscillations are dampened by stabilizing microtubules or by decondensing chromatin, yet inter-chromosomal coordination is preserved. The dissociation between chromosome oscillations and chromosome coordination suggests that coordination can arise from forces transmitted through the spindle environment. To test this idea, we developed a minimal mechanical model in which oscillating chromosome pairs are coupled through transient inter-chromosomal springs, while oscillations of each chromosome pair are generated by feedback between kinetochore-microtubule dynamics and centromere elasticity. The model demonstrates that stochastic mechanical connections are sufficient to generate correlated chromosome motion. To quantify chromosome coordination in a manner that reflects the mechanical properties of the surrounding spindle environment, we employed a microrheology-inspired analysis of time-lagged chromosome displacements. This framework reveals that microtubules and chromatin play distinct mechanical roles: microtubules primarily determine the spatial range and temporal build-up of coordination, while chromatin tunes its strength. Together, our results establish coordinated chromosome motion as an emergent mechanical property of the mitotic spindle, mediated by its viscoelastic properties and collective force transmission.