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Design and operation of reconfigurable two-dimensional DNA molecular arrays

Abstract

Information relay and cascaded transformation are essential in biology and engineering. Imitation of such complex behaviors via synthetic molecular self-assembly at the nanoscale remains challenging. Here we describe the use of structural DNA nanotechnology to realize prescribed, multistep, long-range information relay and cascaded transformation in rationally designed molecular arrays. The engineered arrays provide a controlled platform for studying complex dynamic behaviors of molecular arrays and have a range of potential applications, such as with reconfigurable metamaterials. A reconfigurable array consists of a prescribed number of interconnected dynamic DNA antijunctions. Each antijunction unit consists of four DNA domains of equal length with four dynamic nicking points, which are capable of switching between two stable conformations through an intermediate open conformation. By interconnecting the small DNA antijunctions, one can build custom two-dimensional (2D) molecular ‘domino’ arrays with arbitrary shapes. More important, the DNA molecular arrays are capable of undergoing programmed, multistep, long-range transformation driven by information relay between neighboring antijunction units. The information relay is initiated by the trigger strands under high temperature or formamide concentration. The array’s dynamic behavior can be regulated by external factors such as its shape and size, points of transformation initiation, and/or any engineered information propagation pathways. This protocol provides detailed strategies for designing DNA molecular arrays, as well as procedures for sample production, purification, reconfiguration, and imaging by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The procedure can be completed in 4–7 d.

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Fig. 1: Dynamic DNA antijunction and reconfiguration of DNA arrays driven by trigger strands and information relay through antijunction units.
Fig. 2
Fig. 3: Design of DNA antijunctions and DNA arrays.
Fig. 4: Overview of sample preparation for DNA brick or origami molecular arrays.
Fig. 5: AFM imaging process for in situ transformation.
Fig. 6: Regulation strategies for DNA origami relay arrays.

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Acknowledgements

This work was supported by the NSF (CAREER Award DMR-1654485), the Wallace H. Coulter Department of Biomedical Engineering Startup Fund, a Billi and Bernie Marcus Research Award (to Y.K.), the National Natural Scientific Foundation of China (grants 11761141006 and 21605102 to J.S.), and the National Key Research and Development Program of China (grant 2017FYA0205301 to D.C.).

Author information

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Authors

Contributions

J.S. and Y.K. conceived and led the project. J.S., P.W., and Y.K. designed and conducted the experiments. D.W., J.S., P.W., V.P., Y.Z., D.C., and Y.K. contributed to the writing of the manuscript.

Corresponding authors

Correspondence to Jie Song or Daxiang Cui or Yonggang Ke.

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Competing interests

A provisional US patent application based on the work described in this paper has been filed.

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Article describing the development of the approach

1. Song, J. et al. Science 357, eaan3377 (2017): https://doi.org/10.1126/science.aan3377

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Integrated supplementary information

Supplementary Figure 1

Design diagram of the 11 × 4 52-bp DNA origami array.

Supplementary Figure 2

Design diagram of the 20 × 8 42-bp DNA brick array.

Supplementary information

Supplementary Figures 1 and 2 and Supplementary Tables 1 and 2

Reporting Summary

Supplementary Data 1

Python code for sequence generation

Supplementary Data 2

caDNAno files for the 11 × 4 52-bp DNA origami array and the 20 × 8 42-bp DNA brick array

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Wang, D., Song, J., Wang, P. et al. Design and operation of reconfigurable two-dimensional DNA molecular arrays. Nat Protoc 13, 2312–2329 (2018). https://doi.org/10.1038/s41596-018-0039-0

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