Role of matrix stiffness on adhesion, migration,proliferation and differentiation of HaCaT cells: an in VITRO study

Abstract

Since past few decades, a paradigm shift has been observed in the field of manual tuning of cell behavior using external mechanical cues. In this regard, matrix stiffness is considered as a crucial factor that regulates the cell adhesion, spreading, migration, proliferation and differentiation. The aim of this study was to decipher the role of matrix stiffness on key cellular processes including cell adhesion, spreading and cytoskeletal reorganization at molecular level. To investigate the aforesaid prospective, epithelial cells (HaCaT) were chosen and cultured on silicone based PDMS substrate within a stiffness range from 62 kPa to 855 kPa. Our result showed that extent of initial cell adhesion was higher on softer substrate whereas overall cell adhesion kinetics was faster for stiffer substrate. Cell proliferation was favored on the stiffer substrate as evident from MTT assay, pERK 1/2 expression and its nuclear localization. On the other hand rate of cell migration was higher on the softer substrates due to low E-cadherin expression and subsequent destabilization by â-catenin. Cellular differentiation was analyzed by checking filaggrin expression and our results indicate that stiffer substrate significantly favored the HaCaT cell differentiation. Modulation of such cell behaviors in response to matrix stiffness may prove to be useful for various tissue engineering purposes.