Delamination of epithelia induced by air-liquid interfaces

Many epithelial tissues reside at air-liquid interfaces, as exemplified by the ocular epithelium, oral mucosa, and alveolar epithelium. The epithelial interfacial tension imposes a mechanical challenge to tissue homeostasis. However, the interplay between interfacial properties and homeostasis in biological samples has largely been overlooked due to a lack of suitable measurement methods and theoretical developments. Here, we described a surprising observation in which the surface energy at the cell-air interface is sufficient to delaminate a stratified ocular epithelium from its substrate. We demonstrated that the interfacial tension at the epithelium-fluid interfaces can be measured using a modified Schultz's method. The measured value is conceptually and numerically distinctive from the tensile modulus measured by deformation-based methods, such as micropipette aspiration and tissue surface tensiometers. Furthermore, mechanical analysis at the cell-air-liquid triple line during the delamination process revealed a strain-hardening behavior of the epithelial layers. Finally, perturbations on different junctional protein complexes revealed that epithelial mechanical stability requires a delicate balance among cortical tension, focal adhesion, and cell-liquid interfacial tension. Broadly, the modified Schultz's method can be applied to measuring tissue surface tension, and the delamination phenomenon suggests that surface tension is a crucial contributor to tissue mechanical stability.