Accuracy of directional chemosensing via signaling cascades.

Cells interpret noisy biochemical signals with remarkable precision, raising fundamental questions about the limits of sensing. While receptor-level constraints in chemosensing are well characterized, the role of intracellular signaling remains underexplored. We develop a theoretical framework combining stochastic simulations and analytical methods to quantify the accuracy of spatial gradient detection via readout of the cellular response triggered by a linear signaling cascade. Our analysis reveals striking robustness: directional sensing accuracy is unaffected by cytoplasmic activation rates and remains stable under deactivation rates that are much faster or slower than the rest, a regime frequently observed in natural signaling cascades. This robustness persists under nonlinear output transformations that mimic amplification processes such as actin polymerization. Counterintuitively, under certain conditions, downstream readouts improve directional accuracy by extending the effective integration time set by intracellular dynamics.