High-resolution mapping of bifurcations in nonlinear biochemical circuits

Anthony Genot; A. Baccouche; R. Sieskind; N. Aubert-Kato; N. Bredeche; J. Bartolo; V. Taly; T. Fujii; Y. Rondelez

doi:10.1038/nchem.2544

High-resolution mapping of bifurcations in nonlinear biochemical circuits

Anthony Genot ^{1, 2} A. Baccouche ^{1, 3} R. Sieskind ^{1, 4} N. Aubert-Kato ^{5, 6} N. Bredeche ⁷ J. Bartolo ^{8, 9, 10} V. Taly ^{9, 10, *} T. Fujii ¹ Y. Rondelez ^{1, 4}

* Corresponding author

1 LIMMS - Laboratory for Integrated Micro Mechatronics Systems

2 LAAS-N2IS - Équipe Nano Ingénierie et Intégration des Systèmes

LAAS - Laboratoire d'analyse et d'architecture des systèmes

3 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques

4 Gulliver

5 Ochanomizu University

6 ELSI - Earth-Life Science Institute [Tokyo]

7 ISIR - Institut des Systèmes Intelligents et de Robotique

8 CAMB - Conception et application de molécules bioactives

9 MEPPOT - U1147 - Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique

10 Centre Universitaires des Saints-Pères

Abstract : Analog molecular circuits can exploit the nonlinear nature of biochemical reaction networks to compute low-precision outputs with fewer resources than digital circuits. This analog computation is similar to that employed by gene-regulation networks. Although digital systems have a tractable link between structure and function, the nonlinear and continuous nature of analog circuits yields an intricate functional landscape, which makes their design counter-intuitive, their characterization laborious and their analysis delicate. Here, using droplet-based microfluidics, we map with high resolution and dimensionality the bifurcation diagrams of two synthetic, out-of-equilibrium and nonlinear programs: a bistable DNA switch and a predator-prey DNA oscillator. The diagrams delineate where function is optimal, dynamics bifurcates and models fail. Inverse problem solving on these large-scale data sets indicates interference from enzymatic coupling. Additionally, data mining exposes the presence of rare, stochastically bursting oscillators near deterministic bifurcations.

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Biotechnology

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https://www.hal.inserm.fr/inserm-02299554
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Submitted on : Friday, September 27, 2019 - 6:14:07 PM
Last modification on : Friday, January 10, 2020 - 9:10:10 PM
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High-resolution mapping of bifurcations in nonlinear biochemical circuits

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High-resolution mapping of bifurcations in nonlinear biochemical circuits

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