Viscoelastically tunable substrates elucidate the interface-relaxation-dependent adhesion and assembly behaviors of epithelial cells

Recent progress in mechanobiology sheds light on the regulation of cellular phenotypes by dissipative property matrices, i.e., viscosity, fluidity, and stress relaxation, addition to extensively studied elasticity. However, most researches have focused bulk mechanics, despite cells 2D culture can only interact with matrix interface directly. Here, we impact interfacial viscosity as well elasticity substrates early stage adhesion behaviors epithelial through new material design mechanical characterization. The materials are copolymers ?-caprolactone d,l-lactide photocrosslinked benzophenone. substrate viscoelasticity changes depending polymer molecular weight irradiation time. relaxation were determined atomic force microscopy modes nanoindentation tip-dwelling, respectively. MDCK changed morphologically, ranging from loose beaded assembly more compact spheroids eventual spread monolayer clusters, response change. Such morphological mainly rather than Single-cell tracking identified biphasic motility minimum speed at intermediate time (~350 ms), where showed transitional morphologies between mesenchymal traits. In that level, partially deformed moved around coalesce surrounding cells, eventually assembling into aggregates. These results highlight, unlike conventional hanging-drop technique, an appropriate level is critical for efficient cell aggregate maturation adhesive viscoelastic matrices. This work not elucidates essential parameter migration, but also gives useful tips creating physiologically relevant drug screening platform.