Consecutive feedback-driven constitutional dynamic networks

Biological regulation; DNA hairpin; DNAzyme; Supramolecular chemistry; Systems chemistry; DNA; Article; DNA, Catalytic; Feedback, Physiological; Kinetics; Metabolic Networks and Pathways; Nanotechnology; Nucleic Acid Conformation; Signal Transduction

Abstract :

[en] Cellular transformations are driven by environmentally triggered complex dynamic networks, which include signal-triggered feedback processes, cascaded reactions, and switchable transformations. We apply the structural and functional information encoded in the sequences of nucleic acids to construct signal-triggered constitutional dynamic networks (CDNs) that mimic the functions of natural networks. Using predesigned hairpin structures as triggers, the network generates functional strands, which stabilize one or the other of the constituents of the network, leading to feedback-driven reconfiguration and time-dependent equilibration of the networks. Using structurally designed hairpins, positive-feedback or negative-feedback mechanisms operated by the CDNs are demonstrated. With two predesigned hairpins, the coupled consecutive operations of negative/positive- or positive/positive-feedback cascades are accomplished. The time-dependent composition changes of the networks are well reproduced by chemical kinetics simulations that provide predictive behaviors of the network, under variable auxiliary conditions. Beyond mimicking natural network properties and functions by means of the synthetic nucleic-acid–based CDNs, the systems introduce versatile perspectives for the design of amplified sensors (sensing of miRNA-376a) and the development of logic gate circuits. © 2019 National Academy of Sciences. All Rights Reserved.

Research center :

MolSys - Molecular Systems - ULiège

Disciplines :

Chemistry

Author, co-author :

Yue, Liang; Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 91904, Israel

Wang, Shan; Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 91904, Israel

Wulf, Verena; Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 91904, Israel

Lilienthal, Sivan; Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 91904, Israel

Remacle, Françoise ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de chimie physique théorique

Levine, Raphaël David; Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 91904, Israel

Willner, Itamar; Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 91904, Israel

Language :

English

Title :

Consecutive feedback-driven constitutional dynamic networks

Publication date :

2019

Journal title :

Proceedings of the National Academy of Sciences of the United States of America

ISSN :

0027-8424

eISSN :

1091-6490

Publisher :

National Academy of Sciences

Volume :

116

Issue :

Pages :

2843-2848

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

ISF - Israel Science Foundation [IL]
MPI-PKS - Max-Planck-Institut für Physik Komplexer Systeme
SNF - Schweizerische Nationalfonds zur Förderung der wissenschaftlichen Forschung [CH]

Available on ORBi :

since 05 January 2020

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