Effects of matrix viscoelasticity on cell–matrix interaction, actin cytoskeleton organization, and apoptosis of osteosarcoma MG-63 cells

Abstract

Many recent reports have shown the effects of viscoelasticity of the extracellular matrix on the spreading, migration, proliferation, survival and cell–matrix interaction of mesenchymal stem cells and normal cells. However, the effect of matrix viscoelasticity on the behavior of tumor cells is still in the state of preliminary exploration. To this aim, we prepared a viscoelastic hydrogel matrix with a storage modulus of about 2 kPa and a loss modulus adjustable from 0 to 600 Pa, through adding linear alginate and regulating the compactness of a polyacrylamide covalent network. Overall, the addition of viscous components inhibited the apoptosis of osteosarcoma MG-63 cells, while it promoted their spreading and proliferation and in particular led to a well-developed cytoskeleton organization. However, with the increase of the viscous fraction, this trend was reversed, and the apoptosis of MG-63 cells gradually increased with gradually decreased spreading and proliferation, accompanied by a surprising manner change of the cytoskeleton from fusiform cells dominated by focal adhesion to dendritic cells dominated by pseudopodia. Besides the upregulation of MAPK, Ras, Rap1 and PI3K-Akt pathways commonly involved in mechanotransduction, the upregulation of the Wnt pathway and inhibited endoplasmic reticulum stress-mediated apoptosis were observed for the viscous matrix with a low loss modulus. The high viscosity matrix showed additional involvement of Hippo and NF-kappa B signaling pathways related to the cell–matrix interaction, with downregulation of the endoplasmic reticulum stress pathway and upregulation related to mitochondrial organization. Our study would provide insight into the effect of viscosity on fundamental behaviors of tumor cells and might have important implications in designing antitumor materials.