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

TL;DR

This paper investigates how insulating motifs can reduce retroactivity in biochemical circuits, revealing a trade-off between low fuel consumption and reduced robustness to perturbations.

Contribution

It demonstrates that simple, low-fuel-cost insulating motifs can suppress retroactivity but may weaken network robustness and response speed.

Findings

Insulating motifs can effectively reduce retroactivity with minimal fuel use.

Low coupling in insulating motifs decreases retroactivity but reduces robustness.

Trade-offs exist between retroactivity suppression, fuel efficiency, and network resilience.

Abstract

Retroactivity arises when the coupling of a molecular network $\mathcal{U}$ to a downstream network $\mathcal{D}$ results in signal propagation back from $\mathcal{D}$ to $\mathcal{U}$. 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 $\mathcal{U}$. 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.