High rates of fuel consumption are not required by insulating motifs to suppress retroactivity in biochemical circuits

Retroactivity arises when the coupling of a molecular network to a downstream network results in signal propagation back from to . The phenomenon represents a breakdown in modularity of biochemical circuits and hampers the rational design of complex functional networks. Considering simple models of signal-transduction architectures, the authors demonstrate the strong dependence of retroactivity on the properties of the upstream system, and explore the cost and efficacy of fuel-consuming insulating motifs that can mitigate retroactive effects. They find that simple insulating motifs can suppress retroactivity at a low fuel cost by coupling only weakly to the upstream system . However, this design approach reduces the signalling network's robustness to perturbations from leak reactions, and potentially compromises its ability to respond to rapidly varying signals.