Wetting transitions of cellular aggregates induced by substrate rigidity

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 Ec ≈ 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 = Ec, we observe a wetting transition, and on soft substrates (E < Ec), 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.