Spatiotemporal Oscillation in Confined Epithelial Motion upon Fluid-to-Solid Transition

Fluid-to-solid phase transition in multicellular assembly is crucial in many developmental biological processes, such as embryogenesis and morphogenesis. However, biomechanical studies in this area are limited, and little is known about factors governing the transition and how cell behaviors are regulated. Due to different stresses present, cells could behave distinctively depending on the nature of tissue. Here we report a fluid-to-solid transition in geometrically confined multicellular assemblies. Under circular confinement, Madin-Darby canine kidney (MDCK) monolayers undergo spatiotemporally oscillatory motions that are strongly dependent on the confinement size and distance from the periphery of the monolayers. Nanomechanical mapping reveals that epithelial tensional stress and traction forces on the substrate are both dependent on confinement size. The oscillation pattern and cellular nanomechanics profile appear well correlated with stress fiber assembly and cell polarization. These experimental observations imply that the confinement size-dependent surface tension regulates actin fiber assembly, cellular force generation, and cell polarization. Our analyses further suggest a characteristic confinement size (approximates to MDCK's natural correlation length) below which surface tension is sufficiently high and triggers a fluid-to-solid transition of the monolayers. Our findings may shed light on the geometrical and nanomechanical control of tissue morphogenesis and growth.