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Publications

Journal Article Ppublish

PubMed: 40343993 DOI: 10.1073/pnas.2416659122

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

Proc Natl Acad Sci U S A 122(19):e2416659122

Authors: Aninda Mitra, Marie F A Cutiongco, Romina Burla, Yongpeng Zeng, Qin Na, Mengya Kong, Benjamin Vinod, Mui Hoon Nai, Barbara Hübner, Alexander Ludwig, Chwee Teck Lim, G V Shivashankar, Isabella Saggio, Wenting Zhao

Affiliations

  • School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637457, Singapore.
  • Dipartimento di Biologia e Biotecnologie, Sapienza-Università di Roma, Roma 00185, Italy.
  • Department of Biomedical Engineering, National University of Singapore, Singapore 117583, Singapore.
  • School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
  • NTU Institute of Structural Biology, Nanyang Technological University, Singapore 636921, Singapore.
  • Institute for Health Innovation and Technology, National University of Singapore, Singapore 117599, Singapore.
  • Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
  • Department of Health Sciences and Technology, ETH Zürich, Zürich 8093, Switzerland.
  • Laboratory of Multiscale Bioimaging, Paul Scherrer Institut, Villigen, Aargau 5232, Switzerland.
  • Institute for Digital Molecular Analytics and Science, Nanyang Technological University, Singapore 636921, Singapore.

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.

MeSH

Mechanics, Cells, Heterochromatin, Nuclear Lamina, Neoplasms, Chromatin

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