Encoding signal propagation on topology-programmed DNA origami.

Biological systems often rely on topological transformation to reconfigure connectivity between nodes to guide the flux of molecular information. Here we develop a topology-programmed DNA origami system that encodes signal propagation at the nanoscale, analogous to topologically efficient information processing in cellular systems. We present a systematic molecular implementation of topological operations involving 'glue-cut' processes that can prompt global conformational change of DNA origami structures, with demonstrated major topological properties including genus, number of boundary components and orientability. By spatially arranging reactive DNA hairpins, we demonstrate signal propagation across transmission paths of varying lengths and orientations, and curvatures on the curved surfaces of three-dimensional origamis. These DNA origamis can also form dynamic scaffolds for regulating the spatial and temporal signal propagations whereby topological transformations spontaneously alter the location of nodes and boundary of signal propagation network. We anticipate that our strategy for topological operations will provide a general route to manufacture dynamic DNA origami nanostructures capable of performing global structural transformations under programmable control.

Accelerating DNA computing via freeze-thaw cycling.

DNA computing harnesses the immense potential of DNA molecules to enable sophisticated and transformative computational processes but is hindered by low computing speed. Here, we propose freeze-thaw cycling as a simple yet powerful method for high-speed DNA computing without complex procedures. Through iterative cycles, we achieve a substantial 20-fold speed enhancement in basic strand displacement reactions. This acceleration arises from the utilization of eutectic ice phase as a medium, temporarily increasing the effective local concentration of molecules during each cycle. In addition, the acceleration effect follows the Hofmeister series, where kosmotropic anions such as sulfate (SO42-) reduce eutectic phase volume, leading to a more notable enhancement in strand displacement reaction rates. Leveraging this phenomenon, freeze-thaw cycling demonstrates its generalizability for high-speed DNA computing across various circuit sizes, achieving up to a remarkable 120-fold enhancement in reaction rates. We envision its potential to revolutionize molecular computing and expand computational applications in diverse fields.

Enzyme-Free Nucleic Acid Circuits for Fold-Change Detection.

Fold-change detection is widespread in sensory systems of various organisms. Dynamic DNA nanotechnology provides an important toolbox for reproducing structures and responses of cellular circuits. In this work, we construct an enzyme-free nucleic acid circuit based on the incoherent feed-forward loop using toehold-mediated DNA strand displacement reactions and explore its dynamic behaviors. The mathematical model based on ordinary differential equations is used to evaluate the parameter regime required for fold-change detection. After selecting appropriate parameters, the constructed synthetic circuit exhibits approximate fold-change detection for multiple rounds of inputs with different initial concentrations. This work is anticipated to shed new light on the design of DNA dynamic circuits in the enzyme-free environment.

Multi-Mode Reconfigurable DNA-Based Chemical Reaction Circuits for Soft Matter Computing and Control.

Developing smart material systems for performing different tasks in diverse environments remains challenging. Here, we show that by integrating stimuli-responsive soft materials with multi-mode reconfigurable DNA-based chemical reaction circuits (D-CRCs), it can control size change of microgels with multiple reaction pathways and adapt expansion behaviors to meet diverse environments. We first use pH-responsive intramolecular conformational switches for regulating DNA strand displacement reactions (SDRs). The ability to regulate SDRs with tunable pH-dependence allows to build dynamic chemical reaction networks with diverse reaction pathways. We confirm that the designed DNA switching circuits are reconfigurable at different pH and perform different logic operations, and the swelling of DNA switching circuit-integrated microgel systems can be programmably directed by D-CRCs. Our approach provides insight into building smart responsive materials and fabricating autonomous soft robots.

Optochemical Control of DNA-Switching Circuits for Logic and Probabilistic Computation.

Precise control of DNA-circuit functions facilitates the construction of complex DNA networks to perform sophisticated functions. Inspired by optochemical genetics with high precision for controlling and studying neural networks by photoregulation of membrane receptors, we herein report optochemically controlled DNA switching circuits for regulating computation functions. The DNA-switching circuits involve a CG-C+ triplex-based DNA switch that undergoes structural transition from triplex to duplex states after exposure to UV irradiation due to proton transfer, showing optochemical control. We demonstrate that the DNA-switching circuits enable the regulation of computation functions by optochemical control of the state of the DNA switch, including multiple logic computations and probabilistic computation. We hope this work will broaden DNA-circuit functions and facilitate the construction of complex DNA networks.

Nonlinear Regulation of Enzyme-Free DNA Circuitry with Ultrasensitive Switches.

DNA is used to construct synthetic chemical reaction networks (CRNs), such as inorganic oscillators and gene regulatory networks. Nonlinear regulation with a simpler molecular mechanism is particularly important in large-scale CRNs with complex dynamics, such as bistability, adaptation, and oscillation of cellular functions. Here we introduce a new approach based on ultrasensitive switches as modular regulatory elements to nonlinearly regulate DNA-based CRNs. The nonlinear behavior of the systems can be finely tuned by programmable regulation of the linker length and the ligand binding sites, of which the Hill coefficients (nH) are in the range of 1.00-2.32. By integrating two different strand displacement reactions with low-order nonlinearities (nH ≈ 1.44 and 1.54), we could construct CRNs exhibiting high-order nonlinearities with Hill coefficients of up to ∼2.70. In addition, this could provide an efficient approach for designing CRNs at will with complex chemical dynamics by incorporating our design with previously developed enzyme-free DNA circuits.