Traction force transmission via bioactive matrix hydrogel promotes epithelial collective migration mediated by integrin

Mechanical communications provide physical views to understand cell physiologies at large scale. Cell collective migration occurs often in vivo, of which the role of matrix tension force is largely unknown. Here to mimic in vivo conditions, we applied collective migration of renal epithelial MDCK cells on elastic matrix hydrogel containing bioactive materials of 50% Matrigel and 1 mg/mL type I collagen. MDCK cells were engineered with stable expression of ERK FRET (fluorescence energy resonance transfer) biosensor in regarding of ERK sensitivity in cell mechanical response. The results showed that matrix traction force derived from cells-generated contraction promoted epithelial sheet migration with higher ERK activity at the move front. Hydrogel crosslinking by glutaraldehyde blocked matrix traction transmission and then reduced ERK and epithelial collective migration. Integrin inhibition dramatically reduced collective migration but not local cell moving velocities, indicating integrin acting as mechanical transducer at cells-hydrogel interface in orienting migration direction. Further experiments demonstrated that matrix traction force relied on activations of cellular mechanosensitive calcium and Piezo1 channels, and ERK signal in promoting collective migration. In conclusion, matrix tension force derived from cell contractions facilitates epithelial collective migration through activating cellular mechanosensitive signals, in which integrin acts as mechanical transducer. This work highlights the role of matrix traction force in wound healing and tissue engineering.