AbstractIntercellular junctions are important mechanical couplers between cells in epithelial layers providing adhesion and intercellular communication. Regulation of the junctions occurs in cellular processes such as layer formation, epithelial-to-mesenchymal transition, embryogenesis, and cancer progression. Many studies addressed the role of force generation in cells for establishing lateral cell-cell junctions and the role of cellular force transmission in tissue formation and maintenance. Our atomic force microscopy- (AFM) based study shed light on the role of both, tight junctions and adherens junctions for the mechanical properties of individual epithelial cells that are part of a confluent monolayer. We found that tight junctions are important for the establishment of a functional barrier-forming layer but impairing them does not reduce the mechanical integrity of cells. Depletion of ZO-1 results in a weak increase in cortical tension. An opposite effect was observed for disruption of E-cadherin-mediated adherens junctions using DTT. Opening of adherens junctions leads to substantial alterations of cellular mechanics such as reduced overall stiffness, but these changes turned out to be reversible after re-establishing disulfide bridges in E-cadherin by removal of DTT. We found that regulatory mechanisms exist that preserve mechanical integrity during recovery of disrupted adherens junctions.