Ultrathin Hydrogel Membranes Inspired by Soap Films Enable Physiologically Relevant Breathing Lung Models.

Abstract

Breathing continuously stretches the lungs, providing essential mechanical cues that regulate cellular behavior and disease responses. Mimicking the repetitive out-of-plane deformation of alveolar tissues driven by transpulmonary pressure requires ultrathin stretchable hydrogel membranes that sustain prolonged cyclic loading in hydrated environments. However, membrane thinning inevitably amplifies stress concentration and fatigue failure, making the simultaneous achievement of ultrathin geometry and long-term durability fundamentally incompatible in conventional hydrogel systems. Here, we present a soap film-inspired hydrogel membrane that overcomes this trade-off and enables dynamic breathing lung models. By incorporating acrylamide into gelatin methacryloyl, precursor viscosity and surface tension are systematically tuned to generate ultrathin liquid films governed by Frankel's law, while a hybrid co-polymer network is formed to produce durable, freestanding membranes. Integrated with a negative-pressure bioreactor that reproduces physiological breathing under air-liquid interface culture (10%-15% strain, 12 cycles min^-1), the platform establishes a dynamic lung model with physiologically relevant out-of-plane deformation. Cyclic breathing activates YAP-mediated mechanotransduction, drives tissue and extracellular matrix remodeling, and modulates inflammatory and antiviral responses in an influenza A infection model. This work establishes a physics-guided strategy for engineering ultrathin durable hydrogel membranes and advances mechanically faithful in vitro lung models for mechanobiology and respiratory disease research.