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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.

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Figure 1: Spatial organization controls signal propagation.
Figure 2: Signals propagate along wires of different lengths and orientations.
Figure 3: Design and implementation of a wire crossover.
Figure 4: Elementary logic gates are realized with localized DNA hairpins.
Figure 5: Elementary logic gates are combined into multi-input logic circuits.

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Acknowledgements

The authors thank K. Strauss and L. Ceze for their support in initiating this project and F. Randisi for assistance with oxDNA simulations. This work was supported by National Science Foundation grants CCF-1409831, CCF-1317653 and IIS-1212940 and Office of Naval Research grant N00014-13-1-0880 to G.S. G.C. was partially supported by Microsoft Research Ltd.

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G.C., N.D., R.A.M., A.P. and G.S. designed the experiments and wrote the paper. G.C. performed the experiments. N.D. and A.P. performed the modelling studies.

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Correspondence to Andrew Phillips or Georg Seelig.

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Chatterjee, G., Dalchau, N., Muscat, R. et al. A spatially localized architecture for fast and modular DNA computing. Nature Nanotech 12, 920–927 (2017). https://doi.org/10.1038/nnano.2017.127

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