Effects of dose-response relationships on cellular information transmission

Abstract

Cell signaling systems can transmit information with high precision, despite relying on complex reaction networks and inherently noisy biochemical reactions. To better understand how they achieve this precision, this work focuses on how cells can tune their quantitative steady-state dose-response relationships to improve signaling fidelity. Using a combination of analytic and numerical approaches, we quantify the maximum information that can be transmitted in single-step and multi-step signaling systems under several biologically realistic noise distributions: Gaussian, gamma, constant coeffcient of variation, and binomial. We find that signaling systems transmit more information if their dose-response curves have low baselines, large dynamic ranges, and curve shapes that are well matched to the natural distribution of input signals. For multi-step systems, linear transfer functions typically improve signaling fidelity for all noise levels, consistent with previous work on "dose-response alignment". We also find that switchlike transfer functions transmit a maximum of one bit and are robust to low levels of noise, but fail rapidly with high levels of noise. Simulations of toy signaling systems corroborate these results. Together, these findings provide insight into some cellular design principles that have arisen through evolution and that are widely observed in nature.