The adherens junction (AJ) plays an important role in many collective mechanobiological processes, such as gastrulation, embryonic morphogenesis, and tissue homeostasis. In this study, we construct a coarse-grained Monte Carlo simulation model to probe the mechanical properties of AJs. We confirm that cadherin cluster induced by cooperative trans and cis bindings is responsible for AJ’s strength. Systematic simulations reveal that depending on the AJ’s size, the separation force scales with or decouples with the adhesion area, which can explain the conflicting force–area relations in experiments. Moreover, we find that the separation force can be enhanced not only by inter-membrane trans binding but also by intra-membrane cis binding. This cis strengthening effect can indeed boost AJ’s adhesion strength up to the level of focal adhesions, although cadherin’s affinity is three orders of magnitude lower than that of integrin. This work deepens the current understanding of AJ’s mechanics and may help study its functioning in tissue development and tumor progression.

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