  Epithelial tissues form physically integrated barriers against the external
environment protecting organs from infection and invasion. Within each tissue,
epithelial cells respond to different challenges that can potentially
compromise tissue integrity. In particular, cells collectively respond by
reorganizing their cell-cell junctions and migrating directionally towards the
sites of injury. Notwithstanding, the mechanisms that define the spatiotemporal
scales and driving forces of these collective responses remain poorly
understood. To address this we first analyzed the collective response of
epithelial monolayers to injury and compare the results with different
computational models of epithelial cells. We found that a model that integrates
the mechanics of cells at the cell-cell and cell-substrate interface as well as
contact inhibition of locomotion predicts two key properties of epithelial
response to injury as: 1) local relaxation of the tissue and 2) collective
responses involving the elongation of cells (basal and apical regions) and
extension of cryptic lamellipodia that extend up to < 3 cell diameters from the
site of injury. Our results therefore highlight the integration between
junctional biomechanics, cell substrate adhesion and contact inhibition of
locomotion to guide the rapid collective rearrangements that are required to
preserve the epithelial barrier in response to injury.
