The mechanics of heterotypic cell aggregates: insights from computer simulations

Finite element-based computer simulations are used to investigate a number of phenomena, including tissue engulfment, cell sorting, and checkerboard-pattern formation, exhibited by heterotypic cell aggregates. The simulations show that these phenomena can be driven by a single equivalent force, namely a surface (or interfacial) tension, that results from cytoskeletal components and cell-cell adhesions. They also reveal that tissue engulfment, cell sorting, and checkerboard-pattern formation involve several discernible mechanical features or stages. With the aid of analytical arguments, we identify the conditions necessary for each of these phenomena. These findings are consistent with previous experimental investigations and computer simulations, but pose significant challenges to current theories of cell sorting and tissue engulfment.