The inhibition of tissue spreading is of great interest for medical applications, including the prevention of tumor mass dispersal to avoid cancer propagation. While chemical approaches have previously been reported to control tissue spreading, here we investigate a physical mechanism to inhibit spreading. We study the effect of substrate rigidity on the statics and dynamics of spreading of spheroidal aggregates of cells deposited on fibronectin-coated polydimethylsiloxane (PDMS) and polyacrylamide (PAA) substrates by tuning the elastic modulus E from 0.2 kPa to 1.8 MPa while maintaining a constant chemical environment. On rigid substrates, above a threshold elastic modulus E c z 8 kPa, the aggregate spreads with a cellular monolayer expanding around the aggregate (''complete wetting''). The kinetics of spreading obeys a diffusive law with a diffusion coefficient D(E) presenting a maximum that we interpret theoretically. At E ¼ E c , we observe a wetting transition, and on soft substrates (E < E c ), the aggregate no longer spreads. Instead, it flattens and adopts an equilibrium shape of a spherical cap with a finite contact angle (''partial wetting''). These results provide insight into the relevant physical principles underlying cellular aggregate spreading, a phenomenon of interest in the understanding of tumor spreading and invasion.

Despite extensive knowledge on the mechanisms that drive single-cell migration, those governing the migration of cell clusters, as occurring during embryonic development and cancer metastasis, remain poorly understood. Here, we investigate the collective migration of cell on adhesive gels with variable rigidity, using 3D cellular aggregates as a model system. After initial adhesion to the substrate, aggregates spread by expanding outward a cell monolayer, whose dynamics is optimal in a narrow range of rigidities. Fast expansion gives rise to the accumulation of mechanical tension that leads to the rupture of cell–cell contacts and the nucleation of holes within the monolayer, which becomes unstable and undergoes dewetting like a liquid film. This leads to a symmetry breaking and causes the entire aggregate to move as a single entity. Varying the substrate rigidity modulates the extent of dewetting and induces different modes of aggregate motion: “giant keratocytes,” where the lamellipodium is a cell monolayer that expands at the front and retracts at the back; “penguins,” characterized by bipedal locomotion; and “running spheroids,” for nonspreading aggregates. We characterize these diverse modes of collective migration by quantifying the flows and forces that drive them, and we unveil the fundamental physical principles that govern these behaviors, which underscore the biological predisposition of living material to migrate, independent of length scale.