Cells sense the external environment such as a surface topography and change many cellular functions. Cell nucleus has been proposed to act as a cellular mechanosensor, and the changes in nuclear shape possibly affect the functional regulation of cells. This study demonstrated a large-scale mechanical deformation of the intracellular nucleus using polydimethylsiloxane (PDMS)-based micropillar substrates and investigated the effects of nuclear deformation on migration, proliferation, and differentiation of vascular smooth muscle cells (VSMCs). VSMCs spread completely between the fibronectin-coated pillars, leading to strong deformations of their nuclei resulted in a significant inhibition of the cell migration. The proliferation and smooth muscle differentiation of VSMCs with deformed nuclei were dramatically inhibited on the micropillars. These results indicate that the inhibition of proliferation and VSMC differentiation resulted from deformation of the nucleus with high internal stress, and this type of large-scale nuclear mechanical stress might lead the cells to a “quiescent state”.
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