A spatially localized architecture for fast and modular DNA computing

Abstract

Cells use spatial constraints to control and accelerate the flow of information in enzyme cascades and signalling networks. Synthetic silicon-based circuitry similarly relies on spatial constraints to process information. Here, we show that spatial organization can be a similarly powerful design principle for overcoming limitations of speed and modularity in engineered molecular circuits. We create logic gates and signal transmission lines by spatially arranging reactive DNA hairpins on a DNA origami. Signal propagation is demonstrated across transmission lines of different lengths and orientations and logic gates are modularly combined into circuits that establish the universality of our approach. Because reactions preferentially occur between neighbours, identical DNA hairpins can be reused across circuits. Co-localization of circuit elements decreases computation time from hours to minutes compared to circuits with diffusible components. Detailed computational models enable predictive circuit design. We anticipate our approach will motivate using spatial constraints for future molecular control circuit designs.

Programming Motions of DNA Origami Nanomachines

“…For DNA machines powered by DNA hybridization, their motions were driven by the energy released through the hybridization of two complementary single‐stranded DNA (ssDNA) . Spontaneous transition from an energy state to a lower one can drive the motion of DNA machine, leading to directional locomotion of DNA machine on origami platform.…”

DNA‐Based Chemical Reaction Networks

“…Currently, most DNA circuits face slow operation because of low concentrations of reactants or the diffusion of reactants. To tackle this challenge, DNA circuits have been designed and used on scaffolds or surfaces to improve their efficiency . For example, Engelen et al.…”

“…Chatterjee et al. designed domino DNA circuits on a DNA origami, yielding faster kinetics than that of previous systems …”

Biocomputing with Nanostructures on Lipid Bilayers

“…First, functional nanostructures, such as inorganic nanoparticles and DNA nanostructures, offer beneficial properties that are not accessible from purely molecular systems. DNA origami nanostructures, due to their nanoscale addressability, intrinsic sequence‐programmability, and biocompatibility, can control molecular interactions on their surfaces with high spatial precision . This feature has been exploited to build sophisticated nanodevices, such as logic‐gated nanorobots for delivering molecular cargos and molecular circuit boards for operating fast DNA circuits.…”