Nuclear plasticity of cancerous cells on micropillared surfaces: interest for understanding mechanotransduction of metastatic cells
Résumé
Several years ago, we have shown that strong deformations of cancerous cell bodies can be obtained when osteosarcoma cells are cultured on micropillared substrates and that these alterations also affect the nucleus shape. These strong deformations of cells and of their organelles which don't affect viability and proliferation draw an analogy with the metastatic process. That is why the understanding of cells mechanics and of the related inner forces in this model is essential. Here, we analyse the nuclear deformation on micropillared surfaces of cancer cells. As the deformability of cells is strongly connected with their cytoskeleton dynamics, we combine live imaging and AFM elasticity measurements with treatment with inhibitors of cytoskeleton and LINC complex molecules to decipher the involvement of each cytoskeleton component in the nucleus deformation. In parallel the kinetics of deformation of cancer cells on micropillars is analysed in relation with the chromatin condensation. Our findings confirm that actomyosin microfilaments associated with intermediate filaments and LINC molecules play a major role in this deformation. Microtubules are not always involved depending of the cell type. We also demonstrate that pulling down forces imparted by the cytoskeleton are necessary to promote deformation by changing the chemistry on top or in between interpillar space of pillars by spin coating cell adhesive (PnBA) and repellent polymers (PDMAA).