Directed cell motion in response to an external chemical gradient occurs in many biological phenomena such as wound healing, angiogenesis, and cancer metastasis. Chemotaxis is often characterized by the accuracy, persistence, and speed of cell motion, but whether any of these quantities is physically constrained by the others is poorly understood. Using a combination of theory, simulations, and 3D chemotaxis assays on single metastatic breast cancer cells, we investigate the links among these

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... fferent aspects of chemotactic performance. In particular, we observe in both experiments and simulations that the chemotactic accuracy, but not the persistence or speed, increases with the gradient strength. We use a random walk model to explain this result and to propose that cells' chemotactic accuracy and persistence are mutually constrained. Our results suggest that key aspects of chemotactic performance are inherently limited regardless of how favorable the environmental conditions are. Author summary One of the most ubiquitous and important cell behaviors is chemotaxis: the ability to move in the direction of a chemical gradient. Due to its importance, key aspects of chemotaxis have been quantified for a variety of cells, including the accuracy, persistence, and speed of cell motion. However, whether these aspects are mutually constrained is poorly understood. Can a cell be accurate but not persistent, or vice versa? Here we use theory, simulations, and experiments on cancer cells to uncover mutual constraints on the properties of chemotaxis. Our results suggest that accuracy and persistence are mutually constrained.