Emergent Tissue Stability from Intercellular Bond Dynamics during Cyclic Mechanical Loading

Epithelial tissues are often exposed to cyclic deformations in their physiological environment. The mechanical integrity of epithelial tissues relies on intercellular adhesion proteins which link neighbouring cells and transmit forces across the cellular network. The stability of the intercellular adhesive bonds is critical. Under sustained stress, bond failure leads to cumulative damage that progressively weakens the material and ultimately causes failure at the tissue scale. Although the collective behaviour of adhesion bonds under static loading has been characterised to some extent, their response to dynamic loading remains largely unknown, despite its physiological importance. Here we combine quantitative experiments on MDCK monolayers with analytical and stochastic modeling of slip-bond intercellular linkers to investigate tissue resilience under cyclic loading. We find that cyclic loading significantly prolongs tissue lifetime and deformation before failure compared to constant tension, due to intervals of low stress facilitating bond repair. Our model identifies intrinsic rupture and repair timescales governing adhesion stability, revealing three regimes of tissue behavior: rupture, slow damage accumulation and stable equilibrium. Normalizing loading parameters by the intrinsic molecular timescales collapses experimental and simulated data into universal stability maps. These findings demonstrate that epithelial resilience emerges from stochastic adhesion bond dynamics, providing a predictive framework linking molecular adhesion turnover to macroscopic tissue mechanics under physiological cyclic forces.