The fusion of cell aggregates widely exists during biological processes such as development, tissue regeneration, and tumor invasion. Cellular spheroids (spherical cell aggregates) are commonly used to study this phenomenon. In previous studies, with approximated assumptions and measurements, researchers found that the fusion of two spheroids with some cell type is similar to the coalescence of two liquid droplets. However, with more accurate measurements focusing on the overall shape evolution in this process, we find that even in the previously-regarded liquid-like regime, the fusion process of spheroids can be very different from regular liquid coalescence. We conduct numerical simulations using both standard particulate models and vertex models with both Molecular Dynamics and Brownian Dynamics. The simulation results show that the difference between spheroids and regular liquid droplets is caused by the microscopic overdamped dynamics of each cell rather than the topological cell-cell interactions in the vertex model. Our research reveals the necessity of a new continuum theory for “liquid” with microscopically overdamped components, such as cellular and colloidal systems. Detailed analysis of our simulation results of different system sizes provides the basis for developing the new theory.

At small length-scales, capillary effects are significant, and thus the mechanics of soft material interfaces may be dominated by solid surface stresses or liquid surface tensions. The balance between surface and bulk properties is described by an elasto-capillary length-scale, in which equilibrium interfacial energies are constant. However, at small length-scales in biological materials, including living cells and tissues, interfacial energies are not constant but are actively regulated and driven far from equilibrium. Thus, the balance between surface and bulk properties depends upon the distance from equilibrium. Here, we model the spreading (wetting) of living cell aggregates as ‘active droplets’, with a non-equilibrium surface tension that depends upon internal stress generated by the actomyosin cytoskeleton. Depending upon the extent of activity, droplet surface properties adapt to the mechanics of their surroundings. The impact of this adaptation challenges contemporary models of interfacial mechanics, including extensively used models of contact mechanics and wetting.