scholarly journals Cross-Inhibitor: a time-sensitive molecular circuit based on DNA strand displacement

2020 ◽  
Vol 48 (19) ◽  
pp. 10691-10701
Author(s):  
Chanjuan Liu ◽  
Yuan Liu ◽  
Enqiang Zhu ◽  
Qiang Zhang ◽  
Xiaopeng Wei ◽  
...  
Keyword(s):  
Input Signal ◽  
Dna Nanotechnology ◽  
Strand Displacement ◽  
Important Goal ◽  
Molecular Systems ◽  
Molecular Programming ◽  
Dna Strand Displacement ◽  
Input Signals ◽  
Biochemical Systems ◽  
Dna Strand

Abstract Designing biochemical systems that can be effectively used in diverse fields, including diagnostics, molecular computing and nanomachines, has long been recognized as an important goal of molecular programming and DNA nanotechnology. A key issue in the development of such practical devices on the nanoscale lies in the development of biochemical components with information-processing capacity. In this article, we propose a molecular device that utilizes DNA strand displacement networks and allows interactive inhibition between two input signals; thus, it is termed a cross-inhibitor. More specifically, the device supplies each input signal with a processor such that the processing of one input signal will interdict the signal of the other. Biochemical experiments are conducted to analyze the interdiction performance with regard to effectiveness, stability and controllability. To illustrate its feasibility, a biochemical framework grounded in this mechanism is presented to determine the winner of a tic-tac-toe game. Our results highlight the potential for DNA strand displacement cascades to act as signal controllers and event triggers to endow molecular systems with the capability of controlling and detecting events and signals.

scholarly journals Programming colloidal bonding using DNA strand-displacement circuitry

2020 ◽  
Vol 117 (11) ◽  
pp. 5617-5623 ◽  
Author(s):  
Xiang Zhou ◽  
Dongbao Yao ◽  
Wenqiang Hua ◽  
Ningdong Huang ◽  
Xiaowei Chen ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Thermal Annealing ◽  
Constant Temperature ◽  
Room Temperature ◽  
Dna Nanotechnology ◽  
Structural Transformations ◽  
Temperature Sensitive ◽  
Strand Displacement ◽  
Dna Strand Displacement ◽  
Dna Strand

As a strategy for regulating entropy, thermal annealing is a commonly adopted approach for controlling dynamic pathways in colloid assembly. By coupling DNA strand-displacement circuits with DNA-functionalized colloid assembly, we developed an enthalpy-mediated strategy for achieving the same goal while working at a constant temperature. Using this tractable approach allows colloidal bonding to be programmed for synchronization with colloid assembly, thereby realizing the optimal programmability of DNA-functionalized colloids. We applied this strategy to conditionally activate colloid assembly and dynamically switch colloid identities by reconfiguring DNA molecular architectures, thereby achieving orderly structural transformations; leveraging the advantage of room-temperature assembly, we used this method to prepare a lattice of temperature-sensitive proteins and gold nanoparticles. This approach bridges two subfields: dynamic DNA nanotechnology and DNA-functionalized colloid programming.

scholarly journals A domain-level DNA strand displacement reaction enumerator allowing arbitrary non-pseudoknotted secondary structures

2020 ◽  
Vol 17 (167) ◽  
pp. 20190866 ◽  
Author(s):  
Stefan Badelt ◽  
Casey Grun ◽  
Karthik V. Sarma ◽  
Brian Wolfe ◽  
Seung Woo Shin ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Biophysical Model ◽  
Kinetic Properties ◽  
Strand Displacement ◽  
Natural Connection ◽  
Dna Strand Displacement ◽  
Wide Range ◽  
Dna Strand ◽  
High Level ◽  
Domain Level

Information technologies enable programmers and engineers to design and synthesize systems of startling complexity that nonetheless behave as intended. This mastery of complexity is made possible by a hierarchy of formal abstractions that span from high-level programming languages down to low-level implementation specifications, with rigorous connections between the levels. DNA nanotechnology presents us with a new molecular information technology whose potential has not yet been fully unlocked in this way. Developing an effective hierarchy of abstractions may be critical for increasing the complexity of programmable DNA systems. Here, we build on prior practice to provide a new formalization of ‘domain-level’ representations of DNA strand displacement systems that has a natural connection to nucleic acid biophysics while still being suitable for formal analysis. Enumeration of unimolecular and bimolecular reactions provides a semantics for programmable molecular interactions, with kinetics given by an approximate biophysical model. Reaction condensation provides a tractable simplification of the detailed reactions that respects overall kinetic properties. The applicability and accuracy of the model is evaluated across a wide range of engineered DNA strand displacement systems. Thus, our work can serve as an interface between lower-level DNA models that operate at the nucleotide sequence level, and high-level chemical reaction network models that operate at the level of interactions between abstract species.

scholarly journals Effective design principles for leakless strand displacement systems

2018 ◽  
Vol 115 (52) ◽  
pp. E12182-E12191 ◽  
Author(s):  
Boya Wang ◽  
Chris Thachuk ◽  
Andrew D. Ellington ◽  
Erik Winfree ◽  
David Soloveichik
Keyword(s):  
Design Principle ◽  
Side Reaction ◽  
Biochemical Networks ◽  
Strand Displacement ◽  
Regulatory Pathways ◽  
Molecular Systems ◽  
Dna Strand Displacement ◽  
Gate Circuit ◽  
Energy Penalty ◽  
Dna Strand

Artificially designed molecular systems with programmable behaviors have become a valuable tool in chemistry, biology, material science, and medicine. Although information processing in biological regulatory pathways is remarkably robust to error, it remains a challenge to design molecular systems that are similarly robust. With functionality determined entirely by secondary structure of DNA, strand displacement has emerged as a uniquely versatile building block for cell-free biochemical networks. Here, we experimentally investigate a design principle to reduce undesired triggering in the absence of input (leak), a side reaction that critically reduces sensitivity and disrupts the behavior of strand displacement cascades. Inspired by error correction methods exploiting redundancy in electrical engineering, we ensure a higher-energy penalty to leak via logical redundancy. Our design strategy is, in principle, capable of reducing leak to arbitrarily low levels, and we experimentally test two levels of leak reduction for a core “translator” component that converts a signal of one sequence into that of another. We show that the leak was not measurable in the high-redundancy scheme, even for concentrations that are up to 100 times larger than typical. Beyond a single translator, we constructed a fast and low-leak translator cascade of nine strand displacement steps and a logic OR gate circuit consisting of 10 translators, showing that our design principle can be used to effectively reduce leak in more complex chemical systems.

Five Inputs Code Lock Circuit Design Based on DNA Strand Displacement Mechanism

NANO ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. 1950147 ◽  
Author(s):  
Jixiang Li ◽  
Yurong Li ◽  
Junwei Sun ◽  
Yanfeng Wang
Keyword(s):  
Circuit Design ◽  
Logic Circuit ◽  
Experimental Simulation ◽  
Strand Displacement ◽  
Logical Operation ◽  
Alarm Signal ◽  
Dna Strand Displacement ◽  
Input Signals ◽  
Simulation Results ◽  
Dna Strand

In recent years, the development of biological computers is becoming faster and faster, in order to make the logical operation algorithms of biological computers more mature and stable, a new idea for the code lock logic circuit is proposed based on DNA strand displacement by using the dual-rail method. The code lock is designed by four input signals and one conversion input signal. Only when the four input codes are correct and the conversion signal code is turned on, the password lock will be in open state, otherwise the password lock will produce an alarm signal, stopping outside invasion timely. The information of key is processed to obtain the correct password; finally, the experimental simulation results are obtained by Visual DSD software. The results analysis show that the designed code lock circuit is effective, which may provide a good technical support and a good theoretical basis in biological computers development.

scholarly journals Programming Cell-Free Biosensors with DNA Strand Displacement Circuits

2021 ◽  
Author(s):  
Jaeyoung K. Jung ◽  
Khalid K. Alam ◽  
Julius B. Lucks
Keyword(s):  
Response Times ◽  
Dna Nanotechnology ◽  
Fine Tuning ◽  
Digital Converter ◽  
Strand Displacement ◽  
Design Rules ◽  
Analog To Digital ◽  
Dna Strand Displacement ◽  
Dna Strand ◽  
Molecular Computations

ABSTRACTCell-free biosensors are emerging as powerful platforms for monitoring human and environmental health. Here, we expand the capabilities of biosensors by interfacing their outputs with toehold-mediated strand displacement circuits, a dynamic DNA nanotechnology that enables molecular computation through programmable interactions between nucleic acid strands. We develop design rules for interfacing biosensors with strand displacement circuits, show that these circuits allow fine-tuning of reaction kinetics and faster response times, and demonstrate a circuit that acts like an analog-to-digital converter to create a series of binary outputs that encode the concentration range of the target molecule being detected. We believe this work establishes a pathway to create “smart” diagnostics that use molecular computations to enhance the speed, robustness and utility of biosensors.

scholarly journals Rational design of hidden thermodynamic driving through DNA mismatch repair

2018 ◽  
Author(s):  
Natalie E. C. Haley ◽  
Thomas E. Ouldridge ◽  
Alessandro Geraldini ◽  
Ard A. Louis ◽  
Jonathan Bath ◽  
...  
Keyword(s):  
Rational Design ◽  
Reaction Rates ◽  
Strand Displacement ◽  
Forward Reaction ◽  
Molecular Systems ◽  
Dna Mismatch ◽  
Self Assembling ◽  
Dna Strand Displacement ◽  
Displacement Reactions ◽  
Dna Strand

AbstractRecent years have seen great advances in the development of synthetic self-assembling molecular systems. Designing out-of-equilibrium architectures, however, requires a more subtle control over the thermodynamics and kinetics of reactions. We propose a new mechanism for enhancing thermodynamic drive of DNA strand displacement reactions whilst barely perturbing forward reaction rates - introducing mismatches in an internal location within the initial duplex. Through a combination of experiment and simulation, we demonstrate that displacement rates are strongly sensitive to mismatch location and can be tuned by rational design. By placing mismatches away from duplex ends, the thermodynamic drive for a strand-displacement reaction can be varied without significantly affecting the forward reaction rate. This hidden thermodynamic driving motif is ideal for the engineering of nonequilibrium systems that rely on catalytic control and must be robust to leak reactions.

scholarly journals DNA breathing initiated strand displacement circuits for mimicking ant foraging with nanopore readout

2021 ◽  
Author(s):  
Jinbo Zhu ◽  
Jinglin Kong ◽  
Ulrich Keyser ◽  
Erkang Wang
Keyword(s):  
Single Molecule ◽  
Dna Nanotechnology ◽  
Path Selection ◽  
Strand Displacement ◽  
Initiation Mechanism ◽  
Single Molecule Level ◽  
Sensing Platform ◽  
Dna Strand Displacement ◽  
Dna Strand Exchange ◽  
Dna Strand

Abstract DNA strand displacement reaction is essential for the development of molecular computing based on DNA nanotechnology. Additional DNA strand exchange strategies with high selectivity for input will enable novel complex systems including biosensing applications. Most approaches use bulk readout methods based on fluorescent probes that complicate the monitoring of parallel computations. Herein we propose an autocatalytic strand displacement (ACSD) circuit, which is initiated by DNA breathing and accelerated by seesaw catalytic reaction. The special initiation mechanism of the ACSD circuit enables detection of single base mutations at multiple sites in the input strand with much higher sensitivity than classic toehold-mediated strand displacement. A swarm intelligence model is constructed using the ACSD circuit to mimic foraging behaviour of ants. We introduce a multiplexed nanopore sensing platform to report the output results of a parallel path selection system on the single-molecule level. The ACSD strategy and nanopore multiplexed readout method enhance the toolbox for the future development of DNA computing.

scholarly journals Kinetics of DNA Strand Displacement Systems with Locked Nucleic Acids

2017 ◽  
Vol 121 (12) ◽  
pp. 2594-2602 ◽  
Author(s):  
Xiaoping Olson ◽  
Shohei Kotani ◽  
Bernard Yurke ◽  
Elton Graugnard ◽  
William L. Hughes
Keyword(s):  
Nucleic Acids ◽  
Strand Displacement ◽  
Dna Strand Displacement ◽  
Locked Nucleic Acids ◽  
Dna Strand ◽  
Kinetics Of
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