Large intra-chromosome heterogeneity leads to emergent nonlinear mechanics.

Faithful chromosome segregation during mitosis relies on the formation of compact, individualized chromosomes that withstand drag and spindle-generated forces. Structural failure of mitotic chromosomes under force can disrupt the distribution of genetic material to daughter cells, causing aneuploidy or cancer. The overall mechanical properties of mitotic chromosomes have been suggested to arise from their structural heterogeneity. The magnitude and scale of this heterogeneity have not been measured, leaving its impact on chromosome mechanics unresolved. Here we show that chromosomes are highly mechanically heterogeneous: within one chromosome, the local stiffness can vary by up to two orders of magnitude. This extreme mechanical heterogeneity is exemplified by the centromere, which is an order of magnitude softer than the whole chromosome. These results demonstrate how the mechanical complexity of mitotic chromosomes gives rise to their emergent nonlinear mechanical behaviour, distinct from the polymer properties of their constituents. More broadly, we discuss how structural heterogeneity can shape the nonlinear responses of composite materials, with implications for both understanding biological assemblies and designing new synthetic materials.