Consecutive feedback-driven constitutional dynamic networks

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.