Cell migration at the interface of a dual chemical-mechanical gradient

Cell migration plays a critical role in numerous physiological processes, such as wound healing, response to inflammation, and cancer metastasis. In recent years, accumulating evidence indicates that cell movement is regulated not only by chemical signals but also by mechanical stimuli. In this study, the primary goal is to identify whether a chemical or mechanical stimulus plays the decisive role in directing cell migration. Measuring the motility of cells when they are presented with a combination of chemical and mechanical cues will provide insight into the complex physiological phenomena that guide and direct migration. A novel polyacrylamide hydrogel was designed with an interfacial region where the chemical and mechanical properties varied in opposing directions. One side of the interface was stiff (high Young's modulus) with a low protein concentration, whereas the other side of the interface was compliant (low Young's modulus) with a high protein concentration. The chemical gradient was created by varying the collagen (type I) concentration and the mechanical gradient was introduced by changing the extent of cross-linking in the polymer. The length of the interface with opposing chemical-mechanical profiles was found to be approximately 100 mum. Our results demonstrate that when Balb/c 3T3 fibroblasts were presented with a choice, they either migrated preferentially toward the high-collagen-compliant (low Young's modulus) side of the interfacial region or remained on the high-collagen region, suggesting a more dominant role for chemical stimuli in directing fibroblast locomotion.