Material-Induced Nuclear Deformation Controls Chromatin Architecture in Adipose Stem Cells

The 3D organization of the nucleus is crucial for maintaining cellular homeostasis and function, and it is dynamically regulated by both internal and external forces. Here, we investigate how material-induced cell deformation-generated by engineered micropatterned substrates-influences nuclear morphology and chromatin condensation in adipose-derived stem cells (ASCs). Using a multiscale approach that integrates mechanical modeling, atomic force microscopy (AFM), confocal imaging, and high-resolution analysis, we show that the surface micropatterning modulates intracellular force distributions, which in turn reshape the nuclear envelope and alter chromatin organization. Finite Element simulations reveal that distinct deformation profiles lead to region-specific mechanical stress across the nuclear envelope. These mechanical cues correlate with local chromatin decondensation, as demonstrated by 3D chromatin reconstructions and quantitative morphometric analyses. Our findings demonstrate that cell mechanical perturbations imposed by single-cell micropatterning can shape chromatin architecture and chromosome inter-distances. This opens new avenues for understanding mechanogenomic regulation and designing biomaterials that harness physical cues to control cell behavior.