Enhanced fluctuation of cell prestress on the nomadic culture substrate with stiffness-heterogeneity

Abstract

Mesenchymal stem cell (MSC) is used in clinical application of regenerative cell therapy. However, MSCs deteriorate differentiation ability when mechanical memory of the substrate is accumulated in MSCs. Thus, cell culturing substrate that assure the undifferentiated state of MSCs is required. Since the intracellular stress is considered as the mechanosignal input of the substrate, the culturing substrate that causes the non-steady intracellular stress dynamics should prevent the accumulation of mechanical memory. In this study, by using the micro-elastically patterned hydrogels, we developed cell culture system that activates the fluctuation of intracellular stress. We showed that the fluctuations of the traction force and nuclear shape of MSCs on the triangular patterned gels were significantly larger than those on the homogeneous gels, which came from nomadic motion of the MSCs between soft and stiff regions.