Abstract
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”.
Highlights
Cells sense the external environment and translate this information into biochemical signals that induce various cell responses
These results indicate that the inhibition of proliferation and vascular smooth muscle cells (VSMCs) 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”
The nucleus itself has been proposed to act as a cellular mechanosensor, and the changes in nuclear shape or volume induced by the area controlling cell adhesion possibly affect the regulation of cell proliferation [10] [11]
Summary
Cells sense the external environment and translate this information into biochemical signals that induce various cell responses. Recent studies have suggested that biomechanical cues are important factors for directing cell events, such as cell proliferation [3], differentiation [4], apoptosis [5], and gene expression [6]. The nucleus itself has been proposed to act as a cellular mechanosensor, and the changes in nuclear shape or volume induced by the area controlling cell adhesion possibly affect the regulation of cell proliferation [10] [11]. A present study investigated the effects of nuclear deformation on cellular events, such as cell migration, proliferation, and differentiation using microfabricated cell culture substrates with an array of micropillars. Vascular smooth muscle cells (VSMCs) were used to determine the effects of the micropillar-induced nuclear deformation on normal healthy cells. The migration, proliferation, and contractile differentiation of VSMCs were measured on the micropillar substrates and the effects of a large scale of nuclear deformation with the micropillar substrates on cellular functions were discussed
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