Cell sorting in three dimensions: Topology, fluctuations, and fluidlike instabilities

Previous 2D and 3D models concluded that cell sorting requires cytoskeletal fluctuations and is stalled by high tension at heterotypic interfaces. New deterministic and stochastic models show that this is not true in 3D. Sorting in 3D involves both topological untangling and domain coalescence. Coalescence requires fluctuations and low tension, but untangling does not. It occurs by a Plateau-Rayleigh instability of cell threads-deterministically driven by high tension. At high minority-cell fractions, untangling dominates and significant partial sorting can occur without fluctuations.