Autologous chemotaxis at high cell density

Abstract: Autologous chemotaxis, in which cells secrete and detect molecules to determine the direction of fluid flow, 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 find that it agrees with experimental observations of metastatic cancer cells. To understand this agreement, we derive a physical limit to autologous chemotaxis in terms of the cell density, the P\'eclet number, and the length scales of the cell and its environment. Surprisingly, in an environment that is uniformly oversaturated in the signaling molecule, we find that sensing not only can fail, but can be reversed, causing backwards cell motion. Our results get to the heart of the competition between chemical and mechanical cellular sensing and shed light on a sensory strategy employed by cancer cells in dense tumor environments.