Cross talk between matrix elasticity and mechanical force regulates myoblast traction dynamics

Growing evidence suggests that critical cellular processes are profoundly influenced by the cross talk between extracellular nanomechanical forces and the material properties of the cellular microenvironment. Although many studies have examined either the effect of nanomechanical forces or the material properties of the microenvironment on biological processes, few have investigated the influence of both. Here, we performed simultaneous atomic force microscopy and traction force microscopy to demonstrate that muscle precursor cells (myoblasts) rapidly generate a significant increase in traction when stimulated with a local 10 nN force. Cells were cultured and nanomechanically stimulated on hydrogel substrates with controllable local elastic moduli varying from similar to 16-89 kPa, as confirmed with atomic force microscopy. Importantly, cellular traction dynamics in response to nanomechanical stimulation only occurred on substrates that were similar to the elasticity of working muscle tissue (similar to 64-89 kPa) as opposed to substrates mimicking resting tissue (similar to 16-51 kPa). The traction response was also transient, occurring within 30 s, and dissipating by 60 s, during constant nanomechanical stimulation. The observed biophysical dynamics are very much dependent on rho-kinase and myosin-II activity and likely contribute to the physiology of these cells. Our results demonstrate the fundamental ability of cells to integrate nanoscale information in the cellular microenvironment, such as nanomechanical forces and substrate mechanics, during the process of mechanotransduction.