Fabricating higher-order functional DNA origami structures to reveal biological processes at multiple scales
Source abstract
Abstract
Abstract DNA origami technology enables the precise assembly of well-defined two-dimensional and three-dimensional nanostructures with DNA, an inherently biocompatible material. Given their modularity and addressability, DNA origami objects can be used as scaffolds to fabricate larger higher-order structures with other functional biomolecules and engineer these molecules with nanometer precision. Over the past decade, these higher-order functional structures have shown potential as powerful tools to study the function of various bio-objects, revealing the corresponding biological processes, from the single-molecule level to the cell level. To inspire more creative and fantastic research, herein, we highlight seminal works in four emerging areas of bioapplications of higher-order DNA origami structures: (1) assisting in single-molecule studies, including protein structural analysis, biomolecule interaction analysis, and protein functional analysis, (2) manipulating lipid membranes, (3) directing cell behaviors, and (4) delivering drugs as smart nanocarriers. Finally, current challenges and opportunities in the fabrication and application of DNA origami-based functional structures are discussed.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · Plasmonic and Surface Plasmon Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982).10.1016/0022-5193(82)90002-9 ↗
2. Chandrasekaran, A. R. & Zhuo, R. A ‘tile’ tale: Hierarchical self-assembly of DNA lattices. Appl. Mater. Today 2, 7–16 (2016).10.1016/j.apmt.2015.11.004 ↗
3. Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).10.1038/nature04586 ↗
4. Dey, S. et al. DNA origami. Nat. Rev. Dis. Prim. 1, 13 (2021).
5. Hong, F., Zhang, F., Liu, Y. & Yan, H. DNA origami: scaffolds for creating higher order structures. Chem. Rev. 117, 12584–12640 (2017).10.1021/acs.chemrev.6b00825 ↗
6. Qian, L. et al. Analogic China map constructed by DNA. Chin. Sci. Bull. 51, 2973–2976 (2006).10.1007/s11434-006-2223-9 ↗
7. Andersen, E. S. et al. DNA origami design of dolphin-shaped structures with flexible tails. ACS Nano 2, 1213–1218 (2008).10.1021/nn800215j ↗
8. Douglas, S. M. et al. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 414–418 (2009).10.1038/nature08016 ↗
9. Ke, Y. et al. Multilayer DNA origami packed on a square lattice. J. Am. Chem. Soc. 131, 15903–15908 (2009).10.1021/ja906381y ↗
10. Ke, Y., Voigt, N. V., Gothelf, K. V. & Shih, W. M. Multilayer DNA origami packed on hexagonal and hybrid lattices. J. Am. Chem. Soc. 134, 1770–1774 (2012).10.1021/ja209719k ↗
11. Dietz, H., Douglas, S. M. & Shih, W. M. Folding DNA into twisted and curved nanoscale shapes. Science 325, 725–730 (2009).10.1126/science.1174251 ↗
12. Han, D. et al. DNA origami with complex curvatures in three-dimensional space. Science 332, 342–346 (2011).10.1126/science.1202998 ↗
13. Han, D. et al. DNA gridiron nanostructures based on four-arm junctions. Science 339, 1412–1415 (2013).10.1126/science.1232252 ↗
14. Jun, H. et al. Rapid prototyping of arbitrary 2D and 3D wireframe DNA origami. Nucleic Acids Res. 49, 10265–10274 (2021).10.1093/nar/gkab762 ↗
15. Zhang, F. et al. Complex wireframe DNA origami nanostructures with multi-arm junction vertices. Nat. Nanotechnol. 10, 779–784 (2015).10.1038/nnano.2015.162 ↗
16. Zhang, H. et al. Folding super-sized DNA origami with scaffold strands from long-range PCR. Chem. Commun. 48, 6405–6407 (2012).10.1039/c2cc32204h ↗
17. Chen, X. et al. Self-assembly of large DNA origami with custom-designed scaffolds. ACS Appl. Mater. Interfaces 10, 24344–24348 (2018).10.1021/acsami.8b09222 ↗
18. Marchi, A. N., Saaem, I., Vogen, B. N., Brown, S. & LaBean, T. H. Toward larger DNA origami. Nano Lett. 14, 5740–5747 (2014).10.1021/nl502626s ↗
19. Tikhomirov, G., Petersen, P. & Qian, L. Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns. Nature 552, 67–71 (2017).10.1038/nature24655 ↗
20. Zhou, Y., Dong, J., Zhou, C. & Wang, Q. Finite assembly of three-dimensional DNA hierarchical nanoarchitectures through orthogonal and directional bonding. Angew. Chem. Int. Ed. 61, e202116416 (2022).10.1002/anie.202116416 ↗
21. Seeman, N. C. & Sleiman, H. F. DNA nanotechnology. Nat. Rev. Mater. 3, 17068 (2018).10.1038/natrevmats.2017.68 ↗
22. Iinuma, R. et al. Polyhedra self-assembled from DNA tripods and characterized with 3D DNA-PAINT. Science 344, 65–69 (2014).10.1126/science.1250944 ↗
23. Wang, P. et al. Programming self-assembly of DNA origami honeycomb two-dimensional lattices and plasmonic metamaterials. J. Am. Chem. Soc. 138, 7733–7740 (2016).10.1021/jacs.6b03966 ↗
24. Ye, J., Helmi, S., Teske, J. & Seidel, R. Fabrication of metal nanostructures with programmable length and patterns using a modular DNA platform. Nano Lett. 19, 2707–2714 (2019).10.1021/acs.nanolett.9b00740 ↗
25. Tigges, T., Heuser, T., Tiwari, R. & Walther, A. 3D DNA origami cuboids as monodisperse patchy nanoparticles for switchable hierarchical self-assembly. Nano Lett. 16, 7870–7874 (2016).10.1021/acs.nanolett.6b04146 ↗
26. Wang, Y. et al. DNA origami single crystals with Wulff shapes. Nat. Commun. 12, 3011 (2021).
27. Lin, Z. et al. Engineering organization of DNA nano-chambers through dimensionally controlled and multi-sequence encoded differentiated bonds. J. Am. Chem. Soc. 142, 17531–17542 (2020).10.1021/jacs.0c07263 ↗
28. Yakovchuk, P., Protozanova, E. & Frank-Kamenetskii, M. D. Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Res 34, 564–574 (2006).10.1093/nar/gkj454 ↗
29. Woo, S. & Rothemund, P. W. Programmable molecular recognition based on the geometry of DNA nanostructures. Nat. Chem. 3, 620–627 (2011).10.1038/nchem.1070 ↗
30. Wagenbauer, K. F., Sigl, C. & Dietz, H. Gigadalton-scale shape-programmable DNA assemblies. Nature 552, 78–83 (2017).10.1038/nature24651 ↗
31. Gerling, T., Wagenbauer, K. F., Neuner, A. M. & Dietz, H. Dynamic DNA devices and assemblies formed by shape-complementary, non–base pairing 3D components. Science 347, 1446–1452 (2015).10.1126/science.aaa5372 ↗
32. Yao, G. et al. Meta-DNA structures. Nat. Chem. 12, 1067–1075 (2020).10.1038/s41557-020-0539-8 ↗
33. Huang, C.-M., Kucinic, A., Johnson, J. A., Su, H.-J. & Castro, C. E. Integrated computer-aided engineering and design for DNA assemblies. Nat. Mater. 20, 1264–1271 (2021).10.1038/s41563-021-00978-5 ↗
34. Lan, X. & Wang, Q. DNA-programmed self-assembly of photonic nanoarchitectures. NPG Asia Mater. 6, e97 (2014).
35. Hannewald, N. et al. DNA origami meets polymers: a powerful tool for the design of defined nanostructures. Angew. Chem. Int. Ed. 60, 6218–6229 (2021).10.1002/anie.202005907 ↗
36. Kong, G. et al. DNA origami-based protein networks: from basic construction to emerging applications. Chem. Soc. Rev. 50, 1846–1873 (2021).10.1039/D0CS00255K ↗
37. Stephanopoulos, N. Hybrid nanostructures from the self-assembly of proteins and DNA. Chem. 6, 364–405 (2020).10.1016/j.chempr.2020.01.012 ↗
38. Zhou, K. et al. Toward precise manipulation of DNA-protein hybrid nanoarchitectures. Small 15, e1804044 (2019).10.1002/smll.201804044 ↗
39. Duckworth, B. P. et al. A universal method for the preparation of covalent protein–DNA conjugates for use in creating protein nanostructures. Angew. Chem. Int. Ed. 46, 8819–8822 (2007).10.1002/anie.200701942 ↗
40. Tominaga, J. et al. An enzymatic method for site-specific labeling of recombinant proteins with oligonucleotides. Chem. Commun. 4, 401–403 (2007).10.1039/B613793H ↗
41. Takahara, M., Hayashi, K., Goto, M. & Kamiya, N. Enzymatic conjugation of multiple proteins on a DNA aptamer in a tail-specific manner. Biotechnol. J. 11, 814–823 (2016).10.1002/biot.201500560 ↗
42. Meyer, R. & Niemeyer, C. M. Orthogonal protein decoration of DNA nanostructures. Small 7, 3211–3218 (2011).10.1002/smll.201101365 ↗
43. Nguyen, T. M., Nakata, E., Saimura, M., Dinh, H. & Morii, T. Design of modular protein tags for orthogonal covalent bond formation at specific DNA sequences. J. Am. Chem. Soc. 139, 8487–8496 (2017).10.1021/jacs.7b01640 ↗
44. Saccà, B. et al. Orthogonal protein decoration of DNA origami. Angew. Chem. Int. Ed. 49, 9378–9383 (2010).10.1002/anie.201005931 ↗
45. Chen, R. P., Blackstock, D., Sun, Q. & Chen, W. Dynamic protein assembly by programmable DNA strand displacement. Nat. Chem. 10, 474–481 (2018).10.1038/s41557-018-0016-9 ↗
46. Min, D., Arbing, M. A., Jefferson, R. E. & Bowie, J. U. A simple DNA handle attachment method for single molecule mechanical manipulation experiments. Protein Sci. 25, 1535–1544 (2016).10.1002/pro.2952 ↗
47. Rosier, B. J. H. M. et al. Incorporation of native antibodies and Fc-fusion proteins on DNA nanostructures via a modular conjugation strategy. Chem. Commun. 53, 7393–7396 (2017).10.1039/C7CC04178K ↗
48. Marth, G. et al. Precision templated bottom-up multiprotein nanoassembly through defined click chemistry linkage to DNA. ACS Nano 11, 5003–5010 (2017).10.1021/acsnano.7b01711 ↗
49. Goodman, R. P. et al. A facile method for reversibly linking a recombinant protein to DNA. Chembiochem 10, 1551–1557 (2009).10.1002/cbic.200900165 ↗
50. Shen, W., Zhong, H., Neff, D. & Norton, M. L. NTA directed protein nanopatterning on DNA origami nanoconstructs. J. Am. Chem. Soc. 131, 6660–6661 (2009).10.1021/ja901407j ↗
51. Rosen, C. B. et al. Template-directed covalent conjugation of DNA to native antibodies, transferrin and other metal-binding proteins. Nat. Chem. 6, 804–809 (2014).10.1038/nchem.2003 ↗
52. Ouyang, X. et al. Docking of antibodies into the cavities of DNA origami structures. Angew. Chem. Int. Ed. 56, 14423–14427 (2017).10.1002/anie.201706765 ↗
53. Voigt, N. V. et al. Single-molecule chemical reactions on DNA origami. Nat. Nanotechnol. 5, 200–203 (2010).10.1038/nnano.2010.5 ↗
54. Chhabra, R. et al. Spatially addressable multiprotein nanoarrays templated by aptamer-tagged DNA nanoarchitectures. J. Am. Chem. Soc. 129, 10304–10305 (2007).10.1021/ja072410u ↗
55. Zhou, K., Ke, Y. & Wang, Q. Selective in situ assembly of viral protein onto DNA origami. J. Am. Chem. Soc. 140, 8074–8077 (2018).10.1021/jacs.8b03914 ↗
56. Zhou, K., Zhou, Y., Pan, V., Wang, Q. & Ke, Y. Programming dynamic assembly of viral proteins with DNAorigami. J. Am. Chem. Soc. 142, 5929–5932 (2020).10.1021/jacs.9b13773 ↗
57. Praetorius, F. & Dietz, H. Self-assembly of genetically encoded DNA-protein hybrid nanoscale shapes. Science 355, eaam5488 (2017).10.1126/science.aam5488 ↗
58. Mou, Y., Yu, J. Y., Wannier, T. M., Guo, C. L. & Mayo, S. L. Computational design of co-assembling protein-DNA nanowires. Nature 525, 230–233 (2015).10.1038/nature14874 ↗
59. Buchberger, A., Simmons, C. R., Fahmi, N. E., Freeman, R. & Stephanopoulos, N. Hierarchical assembly of nucleic acid/coiled-coil peptide nanostructures. J. Am. Chem. Soc. 142, 1406–1416 (2020).10.1021/jacs.9b11158 ↗
60. Jin, J. et al. Peptide assembly directed and quantified using megadalton DNA nanostructures. ACS Nano 13, 9927–9935 (2019).10.1021/acsnano.9b04251 ↗
61. Jiang, T. et al. Structurally ordered nanowire formation from co-assembly of DNA origami and collagen-mimetic peptides. J. Am. Chem. Soc. 139, 14025–14028 (2017).10.1021/jacs.7b08087 ↗
62. Udomprasert, A. et al. Amyloid fibrils nucleated and organized by DNA origami constructions. Nat. Nanotechnol. 9, 537–541 (2014).10.1038/nnano.2014.102 ↗
63. Suzuki, Y., Endo, M. & Sugiyama, H. Lipid-bilayer-assisted two-dimensional self-assembly of DNA origami nanostructures. Nat. Commun. 6, 8052 (2015).
64. Dong, Y., Yang, Y., Lin, C. & Liu, D. Frame-guided assembly of amphiphiles. Acc. Chem. Res. 55, 1938–1948 (2022).10.1021/acs.accounts.2c00234 ↗
65. Engelen, W. & Dietz, H. Advancing biophysics using DNA origami. Annu. Rev. Biophys. 50, 469–492 (2021).10.1146/annurev-biophys-110520-125739 ↗
66. Wang, W. et al. Bioapplications of DNA nanotechnology at the solid–liquid interface. Chem. Soc. Rev. 48, 4892–4920 (2019).10.1039/C8CS00402A ↗
67. Zhao, Y. & Xu, C. DNA-based plasmonic heterogeneous nanostructures: building, optical responses, and bioapplications. Adv. Mater. 32, 1907880 (2020).10.1002/adma.201907880 ↗
68. Hu, Y. & Niemeyer, C. M. From DNA nanotechnology to material systems engineering. Adv. Mater. 31, 1806294 (2019).10.1002/adma.201806294 ↗
69. Wickham, S. F. J. et al. Complex multicomponent patterns rendered on a 3D DNA-barrel pegboard. Nat. Commun. 11, 5768 (2020).
70. Funke, J. J. & Dietz, H. Placing molecules with Bohr radius resolution using DNA origami. Nat. Nanotechnol. 11, 47–52 (2016).10.1038/nnano.2015.240 ↗
71. Erben, C. M., Goodman, R. P. & Turberfield, A. J. Single-molecule protein encapsulation in a rigid DNA cage. Angew. Chem. Int. Ed. 45, 7414–7417 (2006).10.1002/anie.200603392 ↗
72. Kahn, J. S., Xiong, Y., Huang, J. & Gang, O. Cascaded enzyme reactions over a three-dimensional, wireframe DNA origami scaffold. JACS Au 2, 357–366 (2022).10.1021/jacsau.1c00387 ↗
73. Martin, T. G. et al. Design of a molecular support for cryo-EM structure determination. Proc. Natl Acad. Sci. 113, E7456–E7463 (2016).
74. Fujita, K., Ohmachi, M., Ikezaki, K., Yanagida, T. & Iwaki, M. Direct visualization of human myosin II force generation using DNA origami-based thick filaments. Nat. Commun. 2, 437 (2019).
75. Seeman, N. C. DNA in a material world. Nature 421, 427–431 (2003).10.1038/nature01406 ↗
76. Zhang, T. et al. 3D DNA origami crystals. Adv. Mater. 30, 1800273 (2018).10.1002/adma.201800273 ↗
77. Tian, Y. et al. Ordered three-dimensional nanomaterials using DNA-prescribed and valence-controlled material voxels. Nat. Mater. 19, 789–796 (2020).10.1038/s41563-019-0550-x ↗
78. Nogales, E. The development of cryo-EM into a mainstream structural biology technique. Nat. Methods 13, 24–27 (2016).10.1038/nmeth.3694 ↗
79. Lyumkis, D. Challenges and opportunities in cryo-EM single-particle analysis. J. Biol. Chem. 294, 5181–5197 (2019).10.1074/jbc.REV118.005602 ↗
80. Aksel, T., Yu, Z., Cheng, Y. & Douglas, S. M. Molecular goniometers for single-particle cryo-electron microscopy of DNA-binding proteins. Nat. Biotechnol. 39, 378–386 (2021).10.1038/s41587-020-0716-8 ↗
81. Zhao, Z. et al. DNA-corralled nanodiscs for the structural and functional characterization of membrane proteins and viral entry. J. Am. Chem. Soc. 140, 10639–10643 (2018).10.1021/jacs.8b04638 ↗
82. Dong, Y. et al. Folding DNA into a lipid-conjugated nanobarrel for controlled reconstitution of membrane. Proteins Angew. Chem. Int. Ed. 57, 2072–2076 (2018).10.1002/anie.201710147 ↗
83. Jones, S. & Thornton, J. M. Principles of protein-protein interactions. Proc. Natl Acad. Sci. 93, 13–20 (1996).10.1073/pnas.93.1.13 ↗
84. Luscombe, N. M., Laskowski, R. A. & Thornton, J. M. Amino acid–base interactions: a three-dimensional analysis of protein–DNA interactions at an atomic level. Nucleic Acids Res 29, 2860–2874 (2001).10.1093/nar/29.13.2860 ↗
85. Cheng, F. et al. Comprehensive characterization of protein–protein interactions perturbed by disease mutations. Nat. Genet. 53, 342–353 (2021).10.1038/s41588-020-00774-y ↗
86. Ryan, D. P. & Matthews, J. M. Protein-protein interactions in human disease. Curr. Opin. Struct. Biol. 15, 441–446 (2005).10.1016/j.sbi.2005.06.001 ↗
87. Garland, W., Benezra, R. & Chaudhary, J. Targeting protein-protein interactions to treat cancer-recent progress and future directions. Annu. Rep. Med. Chem. 48, 227–245 (2013).
88. Scott, D. E., Bayly, A. R., Abell, C. & Skidmore, J. Small molecules, big targets: drug discovery faces the protein–protein interaction challenge. Nat. Rev. Drug Discov. 15, 533–550 (2016).10.1038/nrd.2016.29 ↗
89. Berggård, T., Linse, S. & James, P. Methods for the detection and analysis of protein–protein interactions. Proteomics 7, 2833–2842 (2007).10.1002/pmic.200700131 ↗
90. Ke, Y., Meyer, T., Shih, W. M. & Bellot, G. Regulation at a distance of biomolecular interactions using a DNA origami nanoactuator. Nat. Commun. 7, 10935 (2016).
91. Shaw, A. et al. Binding to nanopatterned antigens is dominated by the spatial tolerance of antibodies. Nat. Nanotechnol. 14, 184–190 (2019).10.1038/s41565-018-0336-3 ↗
92. Le, J. V. et al. Probing nucleosome stability with a DNA origami nanocaliper. ACS Nano 10, 7073–7084 (2016).10.1021/acsnano.6b03218 ↗
93. Funke, J. J., Ketterer, P., Lieleg, C., Korber, P. & Dietz, H. Exploring nucleosome unwrapping using DNA origami. Nano Lett. 16, 7891–7898 (2016).10.1021/acs.nanolett.6b04169 ↗
94. Funke, J. J. et al. Uncovering the forces between nucleosomes using DNA origami. Sci. Adv. 2, e1600974 (2016).10.1126/sciadv.1600974 ↗
95. Nickels, P. C. et al. Molecular force spectroscopy with a DNA origami–based nanoscopic force clamp. Science 354, 305–307 (2016).10.1126/science.aah5974 ↗
96. Kramm, K. et al. DNA origami-based single-molecule force spectroscopy elucidates RNA Polymerase III pre-initiation complex stability. Nat. Commun. 11, 2828 (2020).10.1038/s41467-020-16702-x ↗
97. Aghebat Rafat, A., Sagredo, S., Thalhammer, M. & Simmel, F. C. Barcoded DNA origami structures for multiplexed optimization and enrichment of DNA-based protein-binding cavities. Nat. Chem. 12, 852–859 (2020).10.1038/s41557-020-0504-6 ↗
98. Dutta, P. K. et al. Programmable multivalent DNA-origami tension probes for reporting cellular traction forces. Nano Lett. 18, 4803–4811 (2018).10.1021/acs.nanolett.8b01374 ↗
99. Bustamante, C. J., Chemla, Y. R., Liu, S. & Wang, M. D. Optical tweezers in single-molecule biophysics. Nat. Rev. Dis. Prim. 1, 25 (2021).
100. Pfitzner, E. et al. Rigid DNA beams for high-resolution single-molecule mechanics. Angew. Chem. Int. Ed. 52, 7766–7771 (2013).10.1002/anie.201302727 ↗