Acute chromatin decompaction stiffens the nucleus as revealed by nanopillar-induced nuclear deformation in cells
Abstract
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 low malignancy cancer cell lines (e.g. MCF7, PEO1, A549) but weakened in highly malignant counterparts (e.g. MDA-MB-231, HEYA8, HT1080) due to the capacity to efficiently compact heterochromatin into foci that sustains nucleus deformability required for confined migration. Our work signals how rapid chromatin remodeling is a physiologically relevant pathway to modulate nucleus mechanics and cell migration behavior.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Aninda Mitra
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University
Marie F. A. Cutiongco
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University
Romina Burla
Dipartimento di Biologia e Biotecnologie, Sapienza-Università di Roma
Yongpeng Zeng
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University
Qin Na
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University
Mengya Kong
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University
Benjamin Vinod
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University
Mui Hoon Nai
Department of Biomedical Engineering, National University of Singapore
Barbara Hübner
School of Biological Sciences, Nanyang Technological University
Alexander Ludwig
School of Biological Sciences, Nanyang Technological University
Chwee Teck Lim
Department of Biomedical Engineering, National University of Singapore
G. V. Shivashankar
Department of Health Sciences and Technology, ETH Zürich
Isabella Saggio
Dipartimento di Biologia e Biotecnologie, Sapienza-Università di Roma
Wenting Zhao
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University