Collective effects in flow-driven cancer cell migration

Various cancer cell types have been shown to migrate in the direction of fluid flow via a process called autologous chemotaxis, in which cells secrete and detect molecules that are biased by the flow. This process is thwarted at high cell density because molecules from other cells interfere with a given cell's signal. Using a minimal model of autologous chemotaxis, we determine the cell density at which sensing fails, and we find that it agrees with published experimental measurements. We derive a physical limit to autologous chemotaxis in terms of the cell density, the Péclet number, and the length scales of the cell and its environment. Motivated by the ability of cancer cells to migrate in clusters, we explore the possibility that cells can overcome this physical limit by detecting the flow direction collectively. We demonstrate using theory and simulations that collective autologous chemotaxis is optimal at high cell densities and is realizable using concentration sensing, gradient sensing, and cell-cell repulsion, all ubiquitous cell capabilities. Our results shed light on an important sensory strategy employed by cancer cells in dense tumor environments.