Probing Dynamic Responses of the Extracellular Matrix to Coupled Mechanical and Chemical Inputs

The extracellular matrix (ECM) is an important cellular component that provides structural support for cells that form the various connective tissues in the body and has been linked to various important cellular processes. One major, ubiquitously expressed ECM protein, fibronectin (FN) has been well documented to play an important role in the ECM, but most studies have investigated FN and its assembly and structural organization mainly through chemical stimulation. The ECM though likely experiences multiple modes of stimulation such as mechanical and chemical inputs. Since cells and the ECM may experience mechanical and chemical stimulation, we examined how NIH 3T3 fibroblasts altered their ECM in response to applied mechanical and chemical stimulation. Mechanical stimulation revealed an increase in FN matrix formation and secretion as reflected by immunofluorescence as well as FN localization around the cell periphery. Coupling of mechanical stimulation with chemical stimulation via inhibition of Rho activity revealed the same behavior as cells exposed purely to mechanical stimulation. This study is among the first to show the effect of coupled modes of stimulation on the ECM and show a purely mechanics-induced stimulation of ECM formation. These results have implications in a variety of fields including mechanotransduction, biophysics and bioengineering.