Delamination of epithelia induced by air–liquid interfaces

• Published in: Molecular biology of the cell Vol. 36; no. 8; p. ar90
• Main Authors: Liu, Chunzi, Fuller, Gerald G.
• Format: Journal Article
• Language: English
• Published: United States 01.08.2025
• Subjects: Air; Animals; Biomechanical Phenomena; Epithelial Cells - metabolism; Epithelial Cells - physiology; Epithelium - metabolism; Epithelium - physiology; Focal Adhesions - metabolism; Focal Adhesions - physiology; Humans; Surface Tension
• ISSN: 1059-1524; 1939-4586; 1939-4586
• DOI: 10.1091/mbc.E24-11-0500

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. Many tissues, including skin, eyes, and lungs, are exposed to the air–liquid interface. The surface tension at this interface can alter tissue behaviors, but its role remains unclear due to a lack of measurement methods. Under cell culture conditions, we observed that surface tension can delaminate multilayer epithelia from their substrates. We developed a method to measure surface tension and constructed a phase diagram to predict epithelial behaviors subject to surface tension. The surface tension measurement method is widely applicable to other epithelial tissues. The study suggests that future biomechanical research should consider surface tension while analyzing tissue mechanical stability.