High rates of fuel consumption are not required by insulating motifs to
suppress retroactivity in biochemical circuits
suppress retroactivity in biochemical circuits
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Published version
Author(s)
Deshpande, A
Ouldridge, TE
Type
Journal Article
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.
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.
Date Issued
2017-11-07
Date Acceptance
2017-10-31
Citation
Engineering Biology, 2017, 1 (2), pp.86-99
ISSN
2398-6182
Publisher
IEEE Engineering in Medicine and Biology Society
Start Page
86
End Page
99
Journal / Book Title
Engineering Biology
Volume
1
Issue
2
Copyright Statement
© 2017 The Author(s). This is an open access article published by the IET under the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/3.0/)
Attribution License (http://creativecommons.org/licenses/by/3.0/)
License URL
Sponsor
The Royal Society
Grant Number
UF150067
Subjects
q-bio.MN
q-bio.MN
physics.bio-ph
Notes
25 pages, 19 figures
Publication Status
Published