biostudies-literatureMitra ANanyang Technological University (NTU)MOH | National Medical Research CouncilNational University of SingaporeMinistry of Education - Singapore (MOE)MOH | National Medical Research Council (NMRC)Fondazione AIRC per la ricerca sul cancro ETS (AIRC)Nanyang Technological UniversityFondazione AIRC per la ricerca sul cancro ETSMinistry of Education - SingaporeNational University of Singapore (NUS)e2416659122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12088434biostudies-literatureUnknown122(19)Chromatin architecture is critical in determining nuclear mechanics. Most studies focus on the mechanical rigidity conferred by chromatin condensation from densely packed heterochromatin, but less is known on how transient chromatin decompaction 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 4 h of chromatin decompaction but softened at longer timescales. This acute stiffening of the nucleus was underpinned predominantly by an increase in nucleus volume and nuclear import, and partially by enhanced lamin protein recruitment to the periphery. The coupling between nucleus stiffening and acute chromatin decompaction was observed in loProceedings of the National Academy of Sciences of the United States of AmericaAcute chromatin decompaction stiffens the nucleus as revealed by nanopillar-induced nuclear deformation in cells.PMC12088434Presidential Postdoctoral FellowshipInstitute for Digital Molecular Analytics and Science fundingMOE-MOET32020-0001MOH-001192-01RG145/18 RG93/22 RT3/22Mechanobiology Institute Seed GrantStart-Up Grant NTUitive grant NGF-2021-10-026IG-24614Na QSaggio IKong MNai MHShivashankar GVZhao WZeng YLim CTMitra AHubner BLudwig ACutiongco MFAVinod BBurla RfalseAcute 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 condensation from densely packed heterochromatin, but less is known on how transient chromatin decompaction 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 4 h of chromatin decompaction but softened at longer timescales. This acute stiffening of the nucleus was underpinned predominantly by an increase in nucleus volume and nuclear import, and partially by enhanced lamin protein recruitment to the periphery. The coupling between nucleus stiffening and acute chromatin decompaction was observed in lo2025-01-01T00:00:00Z2025 May2026-06-05T13:38:27.603Z2026-05-17T03:13:03.477ZS-EPMC120884344034399310.1073/pnas.2416659122