The extracellular matrix microtopography drives critical changes in cellular motility and Rho A activity in colon cancer cells

Mechanical signals sent to cells through physical changes in the tumor microenvironment are becoming increasingly understood as important regulators of tumor cell behavior. There is a long history of evaluating the contribution of the topographical features of surfaces on cell behavior in the bioengineering literature. In studies performed to date, the topographical features of a surface have been shown to affect cell adhesion [1-8], migration [2,9], motility [1], survival [10,4], growth [3,11,7], and differentiation [12], with different cell types responding differently to specified textures. These studies have almost uniformly focused on how to bioengineer artificial materials so as to more readily ensure their acceptance in vivo, and as such, have been performed in the context of improving implant and graft survival. In contrast, few studies have been performed evaluating the effect of surface texture, either synthetic or that which has been natively synthesized, on the behavior of malignant cells.Cells change their behavior through the traction forces they exert via their actin cytoskeleton on their surrounding extracellular matrix (ECM) [13]. Investigators studying cell behavior within the pulmonary, cardiovascular, and musculoskeletal system have long understood the importance of mechanical signals to cell behavior and have identified numerous mechanosensing proteins, including the Rho family of proteins. Rho has been shown to regulate traction forces [14,15], to be a critical regulator of intracellular responses to micromechanical properties of the ECM [16-18], to aid in cellular response to physical surroundings in a spatially oriented manner [19], and to be an important regulator of integrins in mechanical tasks of high complexity in three-dimensional surroundings [20]. In addition, these proteins have been linked with epithelial differentiation in response to flexible surroundings [21] as well as to stem cell commitment [22,23].In cancer, Rho has been link