Deshpande, Abhishek, and Thomas E. Ouldridge. “High rates of fuel consumption are not required by insulating motifs to suppress retroactivity in biochemical circuits.” Engineering Biology 1, no. 2 (2017): 86-99.
Retroactivity arises when the coupling of a molecular network U to a downstream network D results in signal propagation back from D to U. 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, we 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. We find that simple insulating motifs can suppress retroactivity at a low fuel cost by coupling only weakly to the upstream system U. 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.