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

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 unresolved. Here, we combine quantitative live-cell imaging in PTK1 cells, targeted perturbations of spindle microtubules and chromatin condensation level, 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 reducing chromatin condensation, yet inter-chromosomal coordination measured by Pearson's correlation coefficient is preserved across all conditions. Consistently, simulations show that Pearson's correlation is insensitive to the mechanical parameters governing inter-chromosomal coupling. Together, these observations motivate the hypothesis that chromosome coordination is a mechanical signature of the physical spindle environment. To test this hypothesis, we develop a minimal mechanical model incorporating transient inter-chromosomal springs as a general representation of inter-chromosomal interactions, and show that they are sufficient to generate correlated chromosome motion. To quantify coordination in a manner that reflects the mechanical properties of the surrounding spindle environment, we used a microrheology-inspired analysis of time-lagged chromosome displacements applied to both experimental and simulated data, revealing that microtubules set the spatial range of coordination while chromatin condensation level modulates its strength. Together, our results support the hypothesis that coordinated chromosome motion is an emergent mechanical property of the mitotic spindle.