Three-dimensional collective cell motions in an acinus-like lumen.

Abstract

Collective cell migration is an essential process in embryo development, wound healing, inflammatory response, and cancer invasion. Although cell motions in two-dimensional (2D) monolayers have been studied previously, three-dimensional (3D) collective cell migration, which constantly occurs during embryogenesis such as the establishment of ducts and acini in vivo, remains elusive. In this paper, we develop a cell-based model incorporating cell mechanics and cell motility to address coherent cell motions in a spherical acinus-like lumen with different cell populations. It is found that the interplays between cell persistence, random fluctuation, and geometrical confinement may engender rich and novel migratory modes. In a 3D spherical lumen, two cells may undergo stripe-like or cross-circular coherent rotations, whereas multiple cells can form dynamic twisting or circulating bands, leaving sparse cells at the center or even a hollow cavity in the cell aggregate. The cell density is found to profoundly influence the collective cell migration modes. Our model can reproduce the fundamental features observed in experiments and highlight the role of mechanics in steering 3D collective cell dynamics during mammary acinar morphogenesis.