Interfacial viscoelastic remodeling of epithelial monolayers analyzed using QCM-D

Epithelial cell layers dynamically remodel their mechanical interactions with the substrate, but the quantitative evaluation of such interfacial behavior remains challenging. Here, we employed quartz crystal microbalance with dissipation (QCM-D) monitoring to investigate how the viscoelastic coupling between epithelial monolayers and their substrate responds to calcium chelation by ethylene glycol tetraacetic acid (EGTA), which disrupts cadherin-mediated cell–cell adhesion and mimics an epithelial–mesenchymal transition (EMT)-like condition. Time-resolved measurements of resonance frequency and energy dissipation were analyzed using a viscoelastic model to extract changes in apparent elastic modulus and damping ratio. EGTA treatment induced a gradual increase in apparent elasticity and a concurrent reduction in viscous damping, reflecting a transition from a strongly coupled viscoelastic state to a partially decoupled and effectively more elastic configuration. The magnitude of these responses increased with culture duration, indicating stronger collective mechanics in more mature cell layers. These findings demonstrate that QCM-D can sensitively detect dynamic alterations in the interfacial mechanical behavior of living cell layers, providing a simple and quantitative platform for investigating EMT-associated transitions and other processes involving collective mechanical remodeling.