Motility-limited aggregation of mammary epithelial cells into fractal-like clusters

Individually migrating cells cluster into multicellular tissues during tissue formation, inflammation, and cancer. The corresponding increase in cell density can result in arrested motion, analogous to the "jamming" of soft materials such as glasses and gels. Here, we show that cells with reduced motility and proliferation organize into branching clusters, reminiscent of aggregation in nonliving colloidal particles. Subsequently, "leader cells" guide collective migration to link clusters together into spanning networks. These arrested dynamics occur at unusually low density and are reminiscent of gelation. Furthermore, increased motility and proliferation recover a glass-like transition at higher density. Overall, arrested motion in living cells has striking similarities with nonliving colloidal particles, suggesting physical signatures of clustering and branching morphogenesis in development and disease.