Cyclic stretch regulates epithelial cell migration in a frequency dependent manner via vinculin recruitment to cell-cell contacts

Abstract

Epithelial cell migration is critical in regulating wound healing and tissue development. The epithelial microenvironment is incredibly dynamic, subjected to mechanical cues including cyclic stretch. While cyclic cell stretching platforms have revealed responses of the epithelium such as cell reorientation and gap formation, few studies have investigated the long-term effects of cyclic stretch on cell migration. We measured the migratory response of the epithelium to a range of physiologically relevant frequencies and stretch. We integrated our experimental approach with high-throughput cell segmentation to discover a relationship between changes in cell morphology and migration as a function of cyclic stretch. Our results indicate that lower stretch frequencies (i.e., 0.1 Hz) arrest epithelial migration, accompanied by cell reorientation and high cell shape solidity. We found that this response is also accompanied by increased recruitment of vinculin to cell-cell contacts, and this recruitment is necessary to arrest cell movements. This work demonstrates a critical role for frequency dependence in epithelial response to mechanical stretch. These results confirm the mechanosensitive nature of vinculin within the adherens junction, but independently reveal a novel mechanism of low frequency stress response in supporting epithelial integrity by arresting cell migration.