Acute chromatin decompaction stiffens the nucleus as revealed by nanopillar-induced nuclear deformation in cells

Chromatin architecture is critical in determining nuclear mechanics. Most studies focus on the mechanical rigidity conferred by chromatin compaction from densely packed heterochromatin, but less is known on how transient changes in chromatin decompaction state impinge on nucleus stiffness. Here, we used an array of vertically aligned nanopillars to study nuclear deformability in situ after chromatin decompaction in cells. The nucleus significantly stiffened within hours of chromatin decompaction but softened at longer timescales. This acute nucleus stiffening was predominantly underlined by an increase in nucleus volume, nuclear import and partially enhanced by lamin protein recruitment to the nuclear periphery. The coupling between nucleus stiffening and acute chromatin decompaction was observed in poorly malignant cancer cell lines but weakened in highly the malignant counterparts due to 0 the capacity to efficiently compact heterochromatin into foci that sustains nucleus deformability required for confined migration. Our work signals how a rapid chromatin remodeling is a physiologically relevant pathway to modulate nucleus mechanics and cell migration behavior.