Abstract
The paper-folding mechanism has been widely adopted in building of reconfigurable macroscale systems because of its unique capabilities and advantages in programming variable shapes and stiffness into a structure1,2,3,4,5. However, it has barely been exploited in the construction of molecular-level systems owing to the lack of a suitable design principle, even though various dynamic structures based on DNA self-assembly6,7,8,9 have been developed10,11,12,13,14,15,16,17,18,19,20,21,22,23. Here we propose a method to harness the paper-folding mechanism to create reconfigurable DNA origami structures. The main idea is to build a reference, planar wireframe structure24 whose edges follow a crease pattern in paper folding so that it can be folded into various target shapes. We realized several paper-like folding and unfolding patterns using DNA strand displacement25 with high yield. Orthogonal folding, repeatable folding and unfolding, folding-based microRNA detection and fluorescence signal control were demonstrated. Stimuli-responsive folding and unfolding triggered by pH or light-source change were also possible. Moreover, by employing hierarchical assembly26 we could expand the design space and complexity of the paper-folding mechanism in a highly programmable manner. Because of its high programmability and scalability, we expect that the proposed paper-folding-based reconfiguration method will advance the development of complex molecular systems.
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Data availability
All relevant data are included in the paper and Supplementary Information. Source data are provided with this paper.
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All relevant code is available from the corresponding author on request.
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Acknowledgements
We thank J. Park for advice on AFM measurement. This research was supported by the National Convergence Research of Scientific Challenges through the National Research Foundation of Korea funded by the Ministry of Science and ICT (no. NRF-2020M3F7A1094299).
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M.K. and D.-N.K. conceived the idea. M.K. and C.L. designed experiments and analysed data. M.K. synthesized DNA wireframe nanostructures. M.K., Y.K. and K.J. conducted fluorescence measurements. M.K. and K.J. performed stimuli-responsive experiments. H.K. and M.C. supported the experimental setup for light irradiation. J.Y.L., M.K. and J.G.L. performed finite element analysis of structures. M.K., K.J., J.Y.L. and D.-N.K. wrote the manuscript.
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D.-N.K. and M.K. are co-inventors on a provisional patent application related to this work filed by Seoul National University R&DB Foundation (no. KR10-2021-0167625, filed 29 November 2021).
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Extended data figures and tables
Extended Data Fig. 1 Synthesis of square DNA wireframe paper.
a, Gel electrophoresis with Ethidium-Bromide stained 1.5wt% agarose gels for 90 min at 75 V by varying the cationic concentration. 12 mM MgCl2 (white box) was used to synthesize square DNA wireframe papers (SQ). b, Representative AFM images of SQ annealed with 12 mM MgCl2 condition. Scale bars, 500 nm and 100 nm.
Extended Data Fig. 2 Detailed crease patterns of SQ folding.
Sky-blue & blue and pink- & yellow-colored edges indicate the DNA wireframe edges with 3′ and 5′ crease handles that could bind with glue1 (G1) and glue2 (G2) strands, respectively. The downward and upward directions of crease handles represent the mountain and valley fold, respectively.
Extended Data Fig. 3 Exemplary AFM images of SQ folding.
Schematic illustration of folded shapes and AFM images. Scale bars, 100 nm.
Extended Data Fig. 4 The procedure of estimating folding yield based on AFM images.
a, Process of estimating the folding yield with an example of SQ (Q1). All particles in the raw AFM image (left) were systematically numbered (middle), filtered depending on their size to remove aggregated particles, and renumbered using customized MATLAB codes (right). Scale bars, 1 μm. b, Partially displayed or irregularly shaped particles were excluded from the yield estimation (red diagonal cancel lines). Individual images with white and red numbers indicate the monomers with intended and unintended shapes, respectively. Scale bar, 100 nm.
Extended Data Fig. 5 Multi-channel miRNA assay through foldable DNA wireframe paper.
a, Schematic illustration of multi-channel miRNA assay using foldable DNA origami. b, Monomer fraction and representative AFM image of each state. Detailed sequence and process to estimate the standard errors are described in Supplementary Table 1. Each sample size is denoted as N. Scale bars, 200 nm.
Extended Data Fig. 6 Larger-size programmable folding system.
a, Schematic illustration of hierarchical assembly of monomeric DNA papers and a folding matrix. b, Modular folding patterns and corresponding numbers. c, Considering the rotation symmetry, 35 cases of larger-size folding systems could be programmed based on a polymeric DNA paper (ABCD) in total.
Extended Data Fig. 7 Detailed crease patterns of larger-scale folding.
Pink- and yellow-colored edges indicate the DNA wireframe edges with 3′ and 5′ crease handles, respectively.
Extended Data Fig. 8 Exemplary AFM images of larger-size folding.
a–j, Exemplary AFM images of diamond (v2), rectangular, right triangle, heart, square, omnibus, ellipse, octagon, house, and open envelope, respectively. Detailed crease patterns are described in Extended Data Fig. 7. Scale bars, 100 nm.
Extended Data Fig. 9 Exemplary procedure of estimating tetramer folding yield based on AFM measurements.
a, Crease pattern and expected configuration of octagon folding after adding glue strands (green arrow). b, Exemplary AFM images of an octagon folding of a larger-size DNA paper. The tetramer folding yield is measured as the number of tetramers with intended folding shapes over the total number of tetramers in AFM images. Individual images with green numbers (right bottom) indicate the successfully folded larger-size DNA papers. Scale bar, 200 nm.
Supplementary information
Supplementary Information
This PDF file contains Supplementary notes on the structural design, mechanical analysis, kinetic model, pH adjustment and cooperative folding of DNA wireframe structures; figures for detailed experimental designs and results with finite element simulation; and tables for quantitative data on folding yields, simulation parameters and staple sequences.
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Kim, M., Lee, C., Jeon, K. et al. Harnessing a paper-folding mechanism for reconfigurable DNA origami. Nature 619, 78–86 (2023). https://doi.org/10.1038/s41586-023-06181-7
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DOI: https://doi.org/10.1038/s41586-023-06181-7
