Probing nanomechanics by direct indentation using Nanoendoscopy-AFM reveals the nuclear elasticity transition in cancer cells

During cancer invasion and metastasis, the mechanical properties of the nucleus change significantly, with reduced elasticity enhancing nuclear deformability to aid cell migration through tight spaces. Traditional methods of measuring nuclear elasticity, such as using bead-attached cantilevers on cells or isolated nuclei, are limited because they also measure the elasticity of surrounding structures, including cell membranes and cytoskeletons. In this study, we used a Nanoendoscopy-atomic force microscope (AFM) with a nanoneedle probe to directly measure nuclear elasticity in living cells. Our findings show that nuclear elasticity increases with serum depletion but decreases when serum-starved cells are treated with TGF-β, which induces epithelial-mesenchymal transition (EMT). In addition, trimethylation levels of histone H4 at lysine 20 but not the expression levels of nuclear lamins positively correlate with these nuclear elasticities. We propose that changes in nuclear elasticity during cancer progression are associated with alterations in chromatin structure.