Motorized chromosome models of mitotic chromosome folding.

Abstract

During mitosis, near-spherical chromosomes reconfigure into rod-like structures to ensure their accurate segregation to daughter cells. We explore here, the interplay between the nonequilibrium activity of molecular motors in determining the chromosomal organization in mitosis and its characteristic symmetry-breaking events. We present a hybrid motorized chromosome model that highlights the distinct roles of condensin I and II in shaping mitotic chromosomes. Guided by experimental observations, the simulations suggest that condensin II facilitates large-scale scaffold formation, while condensin I is paramount in local helical loop arrangement. Together, these two distinct grappling motors establish the hierarchical helical structure characteristic of mitotic chromosomes, which exhibit striking local and, sometimes global, chirality and contribute to the robust mechanical properties of mitotic chromosomes. Accompanying the emergence of rigidity, the model provides mechanisms of forming defects, including perversions and entanglements, and shows how these may be partially resolved through condensin activity and topoisomerase action. This framework bridges coarse-grained energy landscape models of chromosome dynamics and non-equilibrium molecular dynamics, advancing the understanding of chromosome organization during cell division and beyond.