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Integrated computer-aided engineering and design for DNA assemblies

Abstract

Recently, DNA has been used to make nanodevices for a myriad of applications across fields including medicine, nanomanufacturing, synthetic biology, biosensing and biophysics. However, current DNA nanodevices rely primarily on geometric design, and it remains challenging to rationally design functional properties such as force-response or actuation behaviour. Here we report an iterative design pipeline for DNA assemblies that integrates computer-aided engineering based on coarse-grained molecular dynamics with a versatile computer-aided design approach that combines top-down automation with bottom-up control over geometry. This intuitive framework allows for rapid construction of large, multicomponent assemblies from three-dimensional models with finer control over the geometrical, mechanical and dynamical properties of the DNA structures in an automated manner. This approach expands the scope of structural complexity and enhances mechanical and dynamic design of DNA assemblies.

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Fig. 1: Schematic of the proposed design framework for multicomponent DNA origami assemblies.
Fig. 2: Parametric design of functional nanodevices.
Fig. 3: Design of multicomponent complex structures.
Fig. 4: Reconfigurable devices by hierarchical design.
Fig. 5: Broadening the design spectrum by integrating wireframe, lattice and surface-based components.
Fig. 6: Multiscaffold designs.

Data availability

Original data for TEM images and gel electrophoresis are included as Source data. The remaining data supporting the findings of this study are available within the Article and its supplementary information files or available from the corresponding author upon reasonable request.

Code availability

The developed design software MagicDNA is available from GitHub at https://github.com/cmhuang2011/MagicDNA.

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Acknowledgements

This work was supported by National Science Foundation (NSF) grant 1536862 to H.-J.S. and C.E.C. and grant 1921881 to C.E.C. We acknowledge F. Engelhardt and H. Dietz for providing custom scaffolds, T. Aksel and S. Douglas for sharing the caDNAno toolkit, C. Maffeo and A. Aksimentiev for supporting the interface to MrDNA, T. MacCulloch and N. Stephanopoulos for providing K10 peptide and A. Tran, P. Le and P. Lukeman for testing MagicDNA Runtime packages. We thank the Campus Microscopy and Imaging Facility (CMIF) of The Ohio State University for imaging support. We also thank W. Pfeifer and C. Maffeo for critiques on the manuscript and supplementary material. Funding provided by NSF (NSF CMMI) 1536862 and NSF (NSF CMMI) 1921881.

Author information

Authors and Affiliations

Authors

Contributions

C.-M.H. developed the software and the algorithm, designed and simulated all the structures, analysed the data, prepared the tutorial and supported experiments. A.K. conducted the majority of experiments and analysed the experimental results. J.A.J. was an initial user and provided critical early feedback on software features, interface and instructions. H.-J.S. supervised the development of the software and interpreted the data. C.E.C. supervised the experimental validation and the entire study, supported the development of the software and interpreted the data. C.-M.H., A.K., H.-J.S. and C.E.C. wrote the manuscript. All authors commented on and edited the manuscript.

Corresponding authors

Correspondence to Hai-Jun Su or Carlos E. Castro.

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Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Materials thanks Ebbe Andersen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Notes 1–3, Figs. 1–87, Table 1, captions for Videos 1 and 2, and References 1–27.

Supplementary Video 1

Top-down parametric design for a hinge structure performed by converting two lines into bundles and specifying the connectivity to assemble the components.

Supplementary Video 2

The final design profile of the airplane and the CG simulation with 3 × 108 steps.

Supplementary Data 3

The Excel sheets for the staple list of the 14 structures for fabrication.

Supplementary Data 4

Unprocessed gels and gel-intensity analysis for yield determination.

Source data

Source Data Fig. 1

MagicDNA design file and unprocessed TEM image.

Source Data Fig. 2

DNA origami structure raw TEM images.

Source Data Fig. 2d

Source data for motion analysis of 4 bar mechanism.

Source Data Fig. 3

DNA origami structure raw TEM images.

Source Data Fig. 4

DNA origami structure raw TEM images.

Source Data Fig. 6

DNA origami structure raw TEM images and gel electrophoresis image depicting robot arm assembly.

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Huang, CM., Kucinic, A., Johnson, J.A. et al. Integrated computer-aided engineering and design for DNA assemblies. Nat. Mater. 20, 1264–1271 (2021). https://doi.org/10.1038/s41563-021-00978-5

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