Viscocapillary instability in cellular spheroids

Abstract

We describe a viscocapillary instability that can perturb the spherical symmetry of cellular aggregates in culture, also called multicellular spheroids. In the condition where the cells constituting the spheroid get their necessary metabolites from the immediate, outer microenvironment, a permanent cell flow exists within the spheroid from its outer rim where cells divide towards its core where they die. A perturbation of the spherical symmetry induces viscous shear stresses within the tissue that can destabilise the aggregate. The proposed instability is viscocapillary in nature and does not rely on external heterogeneities, such as a pre-existing pattern of blood vessels or the presence of a substrate on which the cells can exert pulling forces. It arises for sufficiently large cell–cell adhesion strengths, cell-renewal rates, and metabolite supplies, as described by our model parameters. Since multicellular spheroids in culture are good model systems of small, avascular tumours, mimicking the metabolite concentration gradients found in vivo, we can speculate that our description applies to microtumour instabilities in cancer progression.