Cell migration underlies many biological processes such as morphogenesis, wound healing, and cancer metastasis. Cell migration tends to occur with directionality in response to external cues. For example, most types of cells migrate along aligned matrix fibers (contact guidance) or preferentially toward stiffer regions (durotaxis), which are often observed during the migration of tumor cells. Although these guided migrations have been modeled in previous studies in various ways, less is known about how cells remodel their surrounding environments to facilitate durotaxis and contact-guided migration for themselves. To address this gap, we developed a biomechanical model with polarized cells contracting and migrating over a fibrous matrix. Using the model, we first confirmed that cells in an externally strained matrix migrate preferentially in the direction of applied external strain. Their migratory patterns were correlated with fiber alignment and stiffness increase induced by the external strain. Then, we showed that cells could remodel a surrounding matrix by applying contractile forces. By analyzing local matrix density, orientation, and tension, we found that some of the cells migrated following aligned fibers that were stiffer than other part of the matrix. Our model provides insight into understanding positive feedback between cell-induced matrix remodeling and migration and the underlying mechanism of cancer metastasis.
Yim et al. (Sun,) studied this question.