Abstract
Sticky-ended cohesion has been the driving force for DNA self-assembly and has enabled model and design programmability in DNA nanotechnology for over 40 years. Traditional units within self-assembled crystals have rationally-designed sticky ends to avoid unpredictable packing behavior, but in doing so, the surprising variety of contact flavors available to natural nucleic acids remains unexploited. Here, we employ composable DNA tiles to form complex 3D architectures using blunt-ended motifs with single duplex interfaces, thereby leveraging the geometry of the tile and the terminal nucleobase identity to control self-assembly outcomes. These crystals yielded X-ray diffraction at resolutions between 10.0 and 1.86 Å. We establish programmability and tunable packing, including translational and inversion symmetries, 5’−3’ and 5’−5’ stacking, and both positive and negative helical twist values. Finally, we establish the ability of racemic mixtures of L- and D-DNA motifs to perform programmable co-assembly driven by terminal π–π interactions, demonstrating molecular recognition and coexistence between mirror molecular systems.
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Acknowledgements
This work was supported by: National Science Foundation grant GCR-2317843 (R.S., J.W.C.); National Science Foundation grant CCF-2505772 (R.S., J.W.C.); Department of Energy Office of Basic Energy Sciences grant DE-SC0007991 (R.S.); National Science Foundation grant DMS-2054321 (N.J.), National Science Foundation grant CCF-2107267 (N.J.); National Science Foundation grant CCF-2505771 (N.J.); and NASA Space Technology Research grant 80NSSC24K1386 (K.W.). The Leica SP8 confocal microscope was purchased with partial support from DMR-1420073 from the MRSEC Program of the National Science Foundation.
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K.W. and S.V. initiated the study. Motifs were designed by K.W. Crystals were prepared by K.W., L.P., S.M., M.J., and J.R. Diffraction was performed by K.W., and structures were solved by A.H. Microscopy was performed by S.V., K.W., and S.M. Supervision was provided by Y.P.O., J.W.C., N.J., S.V., and R.S. The first draft was prepared by S.V., K.W., and A.H. All authors contributed to editing and final draft preparation.
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Woloszyn, K., Horvath, A., Jaffe, M. et al. Blunt-force assembly of programmable DNA architectures using π–π stacking. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69973-1
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DOI: https://doi.org/10.1038/s41467-026-69973-1
