Contact guidance of smooth muscle cells is associated with tension-mediated adhesion maturation

Contact guidance is a cellular phenomenon observed during wound healing and developmental patterning, in which adherent cells align in the same direction due to physical cues. Despite numerous studies, the molecular mechanism underlying the consistent cell orientation is poorly understood. Here we fabricated microgrooves with a pitch of submicrons to study contact guidance of smooth muscle cells. We show that both integrin-based cell-substrate adhesions and cellular tension are necessary to achieve contact guidance along microgrooves. We further show through analyses on paxillin that cell-substrate adhesions are more prone to become mature when they run along microgrooves than align at an angle to the direction of microgrooves. Because cellular tension promotes the maturation of cell-substrate adhesions, we propose that the adhesions aligning across microgrooves are not physically efficient for bearing cellular tension compared to those aligning along microgrooves. Thus, the proposed model describes a mechanism of contact guidance that cells would finally align preferentially along microgrooves because cellular tensions are more easily borne within the direction, and the direction of resulting mature adhesions determines the direction of the whole cells.