Attenuation of noise in ultrasensitive signaling cascades

Abstract

Ultrasensitive cascades often implement thresholding operations in cell signaling and gene regulatory networks, converting graded input signals into discrete all-or-none outputs. However, the biochemical and genetic reactions involved in such cascades are subject to random fluctuations, leading to noise in output signal levels. Here we prove that cascades operating near saturation have output signal fluctuations that are bounded in magnitude, even as the number of noisy cascade stages becomes large. We show that these fluctuation-bounded cascades can be used to attenuate the noise in an input signal, and we find the optimal cascade length required to achieve the best possible noise reduction. Cascades with ultrasensitive transfer functions naturally operate near saturation, and can be made to simultaneously implement thresholding and noise reduction. They are therefore ideally suited to mediate signal transfer in both natural and artificial biological networks.