Highly Deformable Phototunable Viscoelastic Fluid Interface Modulates Cellular Adaptive Wetting Behavior

Abstract Emerging evidence shows that the viscoelastic cues of the e Ixtracellular matrix (ECM) regulate cellular functions and fates. However, as cells are viscoelastic, force dissipation occurs within themselves as well as the ECM side, implying the existence of reciprocal viscous regulation between the two. Here, a fluid‐based scaffold with tunable viscoelasticity has been developed to investigate its impact on the cell adhesion process. The platform is based on the water–perfluorocarbon interface decorated with diacetylene‐based phospholipid membranes (IPLMs), whose viscoelasticity can be systematically manipulated by photocrosslinking. Further introduction of a cell‐adhesive peptide and fluorescent tag allows cell adhesion at the highly deformable fluid interface and confocal observation of dynamic cell–model ECM interactions. The viscoelasticity‐tunability is confirmed by fluorescence recovery after photobleaching, interfacial rheology, and atomic force microscopy nanoindentation. Cells seeded at the IPLM exhibit so‐called adaptive wetting, where the interface first deforms toward the out‐of‐plane direction before cellular dimensional changes, followed by cellular flattening and interfacial restoration. Furthermore, the quantification of these parameters reveals a biphasic response against the crosslinking levels, which indicates that the cell‐ECM viscosity balance determines adaptive wetting phenotypes. The platform may enable the prediction of dynamic adhesion responses in physiological and pathological processes.