Mechanotaxis refers to the directed movement of cell motility via mechanical cues (e.g., fluidic shear stress, substrate stiffness gradients, etc.). In response to fluidic shear stress, for example, cells have been shown to migrate in the direction of the fluid flow. Mechanotaxis is critical in many normal biological processes in animals, such as gastrulation, inflammation, and repair in response to a wound, as well as in mechanisms of diseases such as tumor metastasis. A subset of mechanotaxis - termed durotaxis - refers specifically to cell migration guided by gradients in substrate rigidity (i.e. stiffness). The observation that certain cell types seeded on a substrate rigidity gradient migrate up the gradient (i.e. in the direction of increasing substrate stiffness) was first reported by Lo et al. The primary method for creating rigidity gradients for cells (e.g., in biomaterials) consists of altering the degree of cross-linking in polymers to adjust substrate stiffness. Alternative substrate rigidity gradients include micropost array gradients, where the stiffness of individual microposts is increased in a single, designed direction. History/background There are multiple ways in which a cell’s migration pattern can be influenced, including mechanotaxis, chemotaxis, which is cell movement following a molecular gradient, and haptotaxis, which is cell movement following an adhesion gradient. The first subset of mechanotaxis to be experimentally observed was durotaxis, detailing how contact with a substrate could cause a change in a cell’s migration pattern, but more recently researchers have also examined how contact with a neighboring cell could cause changes in a cell’s migration pattern. Researchers began investigating mechanotaxis of endothelial cells in blood vessels and wound repair in the 1990s and early 2000s. The early 2000s and 2010s also saw more interest in mechanotaxis in the biomedical engineering community as a potential method of cell manipulation. Factors/pathways Cells can detect and react to mechanical stimuli in a variety of ways. One method is through the interaction of E-cadherin presented on the cell membrane. As these receptors interact and are pulled or pushed, tension can be created, leading to a change in the conformation of alpha-catenin bound to B-catenin on the intracellular portion of E-cadherin. This causes the recruitment of vinculin and leads to a change in actin conformation and in the orientation of the cell. Another signaling pathway important in a cell’s response to mechanical stimuli is the Wnt planar cell polarity (PCP) pathway. This noncanonical pathway involves the activation of