Biophysical Society Thematic Meeting | Riga 2026

Active and Responsive Soft Matter: From Biological to Engineered Systems

Poster Abstracts

16-POS Board 16 BRG1/BRM AND COHESIN DIFFERENTIALLY REGULATE NUCLEAR STIFFNESS AND MIGRATION THROUGH CONFINING ENVIRONMENTS Lukasz Suprewicz 1 ; Fitzroy J Byfield 1 ; Thomas T Dutta 1,3 ; Paul A Janmey 1,2 ; 1 University of Pennsylvania, Department of Physiology, Center for Engineering Mechanobiology, Institute for Medicine and Engineering, Philadelphia, PA, USA 2 University of Pennsylvania, Department of Physics & Astronomy, Philadelphia, PA, USA 3 Brown University , Department of Physics, Providence, RI, USA Cell migration through confined environments requires extensive nuclear deformation, making the nucleus a major mechanical barrier during invasion and tissue infiltration. While cytoskeletal forces involved in nuclear deformation are well characterized, the contribution of ATP dependent chromatin remodeling to nuclear mechanics remains less understood. Here, we investigated how inhibition of nuclear ATPases affects nuclear stiffness and confined cell migration. Using isolated karyoplasts from multiple cancer cell lines, fibroblasts, and mesenchymal stem cells, we show that inhibition of the SWI/SNF ATPases BRG1/BRM using BRM014 significantly stiffens nuclei and reduces mechanical dissipation. In contrast, inhibition of cohesin using CIP3TAT softens nuclei and increases dissipation. These opposing mechanical effects strongly correlated with the ability of cells to migrate through confined spaces. BRG1/BRM inhibition markedly reduced migration through micron-sized pores, increased the number of cells trapped within constrictions, and induced persistent nuclear deformation following migration. In contrast, inhibition of cohesin enhanced confined migration in several cancer cell lines. Importantly, both treatments had minimal acute effects on unconstrained 2D motility, suggesting that altered nuclear deformability primarily accounts for the observed migration phenotypes. In 3D collagen matrices, BRG1/BRM inhibition strongly suppressed tumor spheroid invasion, particularly in denser matrices requiring greater nuclear deformation, whereas cohesin inhibition preserved or enhanced invasion. Together, these findings identify nuclear ATPases as key regulators of nuclear mechanics and confined migration and support a model in which continuous chromatin remodeling actively governs nuclear deformability during cell invasion.

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