Cell Dissociations in Collective Invasion

Groups of eukaryotic cells can employ a collective migration strategy for efficiency in many biological processes, including wound healing and cancer invasion. However, confining environments met by cells during migration can lead to cell dissociations, e.g. cancer cells breaking off from an invading tumor front, leading to metastasis. What controls when cells dissociate, and whether they break off singly or in small groups? Can this be determined by cell-cell adhesion or chemotactic cues given to cells? We first design experiments to mimic cancer metastasis using microfluidic devices with microchannels of different widths. Most ruptures are single-cell ruptures, but we observe some ruptures of large groups (~20 cells) in wider channels. The rupture probability is nearly independent of channel width. To better understand the results, we propose a theoretical model with the phase field approach, and recapitulate the experimental results by introducing three different cell types (follower, guided, and a high-motility metabolically active subset of cells) based on their spatial position. These metabolic cells may explain why single-cell rupture is the universal most probable outcome. Our simulation results show that cell-channel adhesion is necessary for cells in narrow channels to invade, and strong cell-cell adhesion leads to fewer but larger ruptures. Chemotaxis also influences the rupture behavior: strong chemotaxis strength leads to larger and faster ruptures. We also study the relation between biological jamming transitions and cell dissociations. Our results suggest unjamming is necessary but not sufficient to create ruptures.