Autologous chemotaxis at high cell density.

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 we 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 Péclet number, and the lengthscales of the cell and its environment. Surprisingly, in an environment that is uniformly oversaturated in the signaling molecule, we find that not only can sensing fail, but it can be reversed, causing backwards cell motion. Our results get to the heart of the competition between chemical and mechanical cellular sensing, and they shed light on a sensory strategy employed by cancer cells in dense tumor environments.

Precision of Flow Sensing by Self-Communicating Cells.

Metastatic cancer cells detect the direction of lymphatic flow by self-communication: they secrete and detect a chemical which, due to the flow, returns to the cell surface anisotropically. The secretion rate is low, meaning detection noise may play an important role, but the sensory precision of this mechanism has not been explored. Here we derive the precision of flow sensing for two ubiquitous detection methods: absorption vs reversible binding to surface receptors. We find that binding is more precise due to the fact that absorption distorts the signal that the cell aims to detect. Comparing to experiments, our results suggest that the cancer cells operate remarkably close to the physical detection limit. Our prediction that cells should bind the chemical reversibly, not absorb it, is supported by endocytosis data for this ligand-receptor pair.