Failure behavior of contractile cell monolayer

Complex biological processes often emerge from coordinated behaviors in microscale cellular organizations. While such systems may involve intricate biochemical pathways and feedback loops, some phenomena can be understood through classical mechanics. One example is the failure of a contractile cell sheet we study here during enzymatic detachment, which resembles fracture of soft elastic films. Upon Trypsin treatment, confluent C2C12 monolayers develop cracks that propagate under the combined influence of intracellular contractile stress and differential cell–substrate detachment. By integrating multiple experimentally characterized parameters — including local cell alignment, contraction direction, contraction magnitude, initial cracks, and anchor sites — we developed a continuum viscoelastic model that reproduces this process in silico. Two metrics, crack area fraction and specific edge length, were introduced to quantitatively describe the failure evolution and evaluate the model performance. Through extensive parametric analysis, our model successfully captured the fracture dynamics of both ordered and disordered cell sheets, as well as other contractile systems such as BMSCs. Despite its simplicity, the model provides a powerful computational framework to investigate collective cell mechanics. Moreover, studying the failure process offers new insights into cell–cell interactions and contractile behaviors, which are fundamental to tissue morphogenesis, regeneration, and engineering.