Nonlinear mechanics of human mitotic chromosomes*

In preparation for mitotic cell division, the nuclear DNA of human cells is compacted into individualized X-shaped metaphase chromosomes. This dramatic metamorphosis has been observed using microscopy for over a century, and yet remarkably little is known about the structural organization of a metaphase chromosome. Here, we probe chromosome organization via force-extension experiments in a novel optical trap set-up. We find that under increasing mechanical load, chromosomes exhibit nonlinear stiffening behavior, distinct from classical polymer models. To explain this anomalous stiffening, we introduce a Hierarchical Worm-like Chain (HWLC) model that describes the chromosome as a heterogeneous assembly of worm-like chains (WLCs).  In this framework, the collective stiffening behaviour of a HWLC is attributed to the broad distribution of the mechanical properties of the assembly components. Finally, we propose that studying the mechanical response of protein degraded or disease-associated chromosomes could lead to new insight on chromosomal organization.