Suppressing collective cell motion with bidirectional guidance cues

In natural environments, cells move in the presence of multiple physical and chemical guidance cues. Using a model system for such guided cell migration, Dictyostelium discoideum (Dicty), we investigate how chemical and physical signals compete in guiding the motion of cell groups. In Dicty cells, chemical signals can lead to collective streaming behavior, in which cells follow one another head-to-tail and aggregate into clusters of similar to 105 cells. We use experiments and numerical simulations to show that streaming and aggregation can be suppressed by the addition of a physical guidance cue of comparable strength to the chemical signals, parallel nanoridges. The bidirectional character of physical guidance by ridges is a determining factor in the suppression of streaming and aggregation. Thus, combining multiple types of guidance cues is a powerful approach to trigger or explain a broad range of collective cell behaviors.