Microtopography-Induced Nuclear Deformation Triggers Chromatin Reorganization and Cytoskeleton Remodeling

Abstract

Cells can adapt to diverse topographical substrates through contact guidance, which regulates the cellular and nuclear morphologies and functions. How adaptive deformation of the cell body and nucleus coordinates to protect genetic material within mechanical microenvironments remains poorly understood. In this study, we engineered micrometer-level narrow-spacing micropillars to mimic constricted extracellular topographies in vivo, enabling us to explore variances in the nuclear architecture, cytoskeleton distribution, and chromatin conformation. The results showed that the area and volume of cell nuclei were distinctly smaller on micropillar topography. Actin and vimentin densely encapsulated the micropillars surrounding the nucleus, effectively segregating it from the micropillars. Additionally, nucleo-cytoskeleton lamin A/C exhibited a polarized distribution at the protrusion of the deformed nuclei. Notably, the degree of heterochromatin was altered in response to significant nuclear deformation, leading to a downregulation trend in H3K9me3 expression. These findings suggest that mechanical constraints imposed by microtopography profoundly influence cell behaviors, providing insights into disease diagnosis and therapeutic interventions in vivo.