Cell physiology is regulated extensively by biochemical factors. However, recent studies have identified many types of mechanosensitive cells to address the importance of mechanical cues in cell functions and motility. While extensive work exists on the effect of adhesive proteins on cells motility, little is known about how motility of cells is affected by the mechanical properties of their physical environment. The effects of substrate stiffness on the morphology and motility speed of 3 different cells have been investigated. Human dermal fibroblast, human keratinocyte HaCaT cell and human aortic endothelial cell (HAEC) were plated onto PDMS of varying stiffness, ranging from 10 kPa to 1 MPa, and coated with the fibronectin. Our results show that there is an optimal migration stiffness range of each cell type. The modulation of mechanical cues such as altering the rigidity of cell environment may be the key mechanism used to regulate cell migration and wound healing.