Page 112 - Read Online

Page 6 of 25 Zhong et al. Chem Synth 2023;3:27 https://dx.doi.org/10.20517/cs.2023.15

Figure 3. Left panel: Nucleic-acid-based feedforward network driven by mismatch-induced competitive strand displacement reactions;
Right panel: The time-dependent relative fluorescence intensity changes of different components in the feedforward network. The right
panel of Figure 3 is quoted with permission from Haley et al. [77] .

FF' in CDN S and GG' in CDN T are modified with two different Mg -ion-dependent DNAzymes as signal
2+
activator units. EE' in CDN S and HH' in CDN T are functionalized with a double-loop region that, in the
presence of an appropriate trigger, can form a triplex structure and act as a signal receptor subunit,
respectively. The two independent networks do not share components and lack communication without
appropriate triggers. Subjecting CDN S and CDN T to two hairpin triggers, H and H leads to the
EE',
HH'
cleavage of H by FF' and H by GG', respectively. The resulting fragmented strand H HH'-1 from the
EE'
HH'
cleavage of H is inclined to bind the signal receptor HH' of CDN T by forming a T-A·T triplex structure.
HH'
It leads to the adaptive upregulation of HH' and GG' and downregulation of GH' and HG' in CDN T.
Meanwhile, H , generated from the GG'-induced cleavage of H , can stabilize EE' in CDN S, resulting in
EE'-1
EE'
the adaptive reconfiguration of CDN S where EE' and FF' are upregulated, and EF' and FE' are
downregulated. In short, the molecular signals communicate between two CDNs to regulate each other. The
intercommunicating CDNs can act as modules for triggered, network-driven, and biocatalytic cascades and
for the intercommunication of network-guided biocatalytic cascades [80,81] .
FAR-FROM-EQUILIBRIUM SIGNAL DYNAMICS
As an open system, life is operated in a far-from-equilibrium manner, which requires a continuous inflow of
external matter and energy to maintain its living functions . Far-from-equilibrium dynamic behaviors are
[82]
[83]
ubiquitous at all levels of biological processes , from molecule-fueled signal transduction , dissipative
[84]
self-assembly of microtubules , and the contraction of muscle cells to the propagation of organisms .
[86]
[85]
Substantial efforts were directed at developing far-from-equilibrium networks to achieve spatiotemporal
biological transformations [87-89] . This section presents recent advances in designing nucleic acid-based far-
from-equilibrium networks for spatiotemporal signaling dynamics. It should be noted that the natural far-
from-equilibrium systems are highly complex. Currently, it is far from able to design a network close to the
complexity of the natural system.

Dissipative behaviors in networks
The organization of a high-ordered living system from disordered non-living components is accompanied
by energy dissipation and entropy production . Such energy dissipation leads to the transient formation of
[90]
active structures in the living system and plays a vital role in characterizing the emerging system and its
resulting properties [91-92] . Substantial research efforts have been directed toward designing an artificial
dissipative network leading to adaptable systems with outstanding features [88-90,92-94] . Constructing a
dissipative network needs the network to be initiated in an inactive state where reactions or interactions of
the network are deactivated. And a fuel-driven network activation mechanism and a following fuel-