Structural Integrity and Relaxation Dynamics of Axially Stressed Chromosomes

Micromechanical studies of mitotic chromosomes have revealed them to be remarkably extensible objects and informed early models of mitotic chromosome organization. We use a data-driven, coarse-grained polymer modeling approach, capable of generating ensembles of chromosome structures that are quantitatively consistent with experiments, to explore the relationship between the spatial organization of individual chromosomes and their emergent mechanical properties. In particular, we investigate the mechanical properties of our model chromosomes by axially stretching them. Simulated stretching led to a linear force-extension curve for small strain, with mitotic chromosomes behaving about ten-fold stiffer than interphase chromosomes. Studying the relaxation dynamics we found that chromosomes are viscoelastic solids, with a highly liquid-like, viscous behavior in interphase that becomes solid-like in mitosis. This emergent mechanical stiffness in our model originates from lengthwise compaction, an effective potential capturing the activity of loop-extruding SMC complexes. Chromosomes denature under large strains via unraveling, which is characterized by the opening of large-scale folding patterns. By quantitatively exploring the mechanical properties of chromosome structural features responsible for various patterns observed in ensemble-averaged contact (HiC) maps, our model provides a nuanced understanding of in vivo mechanics of chromosomes.