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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., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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 (SO 4 ) 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.2- ) 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.

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 ( n H ≈ 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.n H ≈ 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.

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. [ABSTRACT FROM AUTHOR]

During the past decade, DNA computing has been rapidly developed and made continuous progress. Based on typical DNA functional motifs, DNA computational devices can perform diverse powerful computational functions, such as simple Boolean logics and sophisticated neural network algorithms. Thus, DNA computer is widely regarded as one of the most excellent next-generation molecular computers performing Boolean logic. Benefiting from DNAs' inherent properties of biocompatibility, low-cost, ease of synthesis, and sequence programmability, DNA computational devices have shown great potential in various biosensing applications. In this review, we summarize the recent progress in DNA computational devices-based biosensors. Initially, DNA logic circuit-based in vitro biosensing is outlined. Afterwards, the DNA neural network-based in vitro biosensing is reviewed. Further, employing DNA logical circuits for in vivo biosensing and programming cell behaviors is also elaborated. Finally, we discuss future challenges and offer some insights on potential directions of DNA computational device-based smart biosensors. • DNA logic circuit for in vitro biosensing.. • DNA neural network for in vitro biosensing. • DNA logical circuits for in vivo biosensing and programming cell behaviors. [ABSTRACT FROM AUTHOR]