In nature, DNA molecules carry the hereditary information. But DNA has physical and chemical properties that make it attractive for uses beyond heredity. In this Review, we discuss the potential of DNA for creating machines that are both encoded by and built from DNA molecules. We review the main methods of DNA nanostructure assembly, describe recent advances in building increasingly complex molecular structures and discuss strategies for creating machine-like nanostructures that can be actuated and move. We highlight opportunities for applications of custom DNA nanostructures as scientific tools to address challenges across biology, chemistry and engineering.
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Huang, P.-S., Boyken, S. E. & Baker, D. The coming of age of de novo protein design. Nature 537, 320–327 (2016).
Le Poul, N. & Colasson, B. Electrochemically and chemically induced redox processes in molecular machines. Chem. Electro. Chem. 2, 475–496 (2015).
Astumian, R. D. Optical vs. chemical driving for molecular machines. Faraday Discuss. 195, 583–597 (2016).
Sauvage, J.-P. From chemical topology to molecular machines (nobel lecture). Angew. Chem. Int. Ed. 56, 11080–11093 (2017).
Stoddart, J. F. Mechanically interlocked molecules (mims)—molecular shuttles, switches, and machines (nobel lecture). Angew. Chem. Int. Ed. 56, 11094–11125 (2017).
Cheng, C. & Stoddart, J. F. Wholly synthetic molecular machines. Chem. Phys. Chem. 17, 1780–1793 (2016).
Coskun, A., Banaszak, M., Astumian, R. D., Stoddart, J. F. & Grzybowski, B. A. Great expectations: can artificial molecular machines deliver on their promise? Chem. Soc. Rev. 41, 19–30 (2012).
Pezzato, C., Cheng, C., Stoddart, J. F. & Astumian, R. D. Mastering the non-equilibrium assembly and operation of molecular machines. Chem. Soc. Rev. 46, 5491–5507 (2017).
Astumian, R. D. Trajectory and cycle-based thermodynamics and kinetics of molecular machines: the importance of microscopic reversibility. Acc. Chem. Res. 51, 2653–2661 (2018).
Goychuk, I. Molecular machines operating on the nanoscale: from classical to quantum. Beilstein J. Nanotechnol. 7, 328–350 (2016).
Reimann, P. Brownian motors: noisy transport far from equilibrium. Phys. Rep. 361, 57–265 (2002).
Astumian, R. D., Mukherjee, S. & Warshel, A. The physics and physical chemistry of molecular machines. Chem. Phys. Chem. 17, 1719–1741 (2016).
Ranallo, S., Porchetta, A. & Ricci, F. DNA-based scaffolds for sensing applications. Anal. Chem. 91, 44–59 (2019).
Harroun, S. G. et al. Programmable DNA switches and their applications. Nanoscale 10, 4607–4641 (2018).
Tang, Y., Ge, B., Sen, D. & Yu, H.-Z. Functional DNA switches: rational design and electrochemical signaling. Chem. Soc. Rev. 43, 518–529 (2014).
Wang, F., Liu, X. & Willner, I. DNA switches: from principles to applications. Angew. Chem. Int. Ed. 54, 1098–1129 (2015).
Gore, J. et al. DNA overwinds when stretched. Nature 442, 836–839 (2006).
Smith, S. B., Cui, Y. & Bustamante, C. Overstretching B-DNA: the elastic response of individual double-stranded and single-stranded DNA molecules. Science 271, 795–799 (1996).
Hagerman, P. J. Flexibility of DNA. Annu. Rev. Biophys. Biophys. Chem. 17, 265–286 (1988).
Chuang, H. M., Reifenberger, J. G., Cao, H. & Dorfman, K. D. Sequence-dependent persistence length of long DNA. Phys. Rev. Lett. 119, 227802 (2017).
Pfitzner, E. et al. Rigid DNA beams for high-resolution single-molecule mechanics. Angew. Chem. Int. Ed. Engl. 52, 7766–7771 (2013).
Gittes, F., Mickey, B., Nettleton, J. & Howard, J. Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape. J. Cell Biol. 120, 923–934 (1993).
SantaLucia, J. Jr. & Hicks, D. The thermodynamics of DNA structural motifs. Annu. Rev. Biophys. Biomol. Struct. 33, 415–440 (2004).
Zadeh, J. N. et al. NUPACK: analysis and design of nucleic acid systems. J. Comput. Chem. 32, 170–173 (2011).
Trads, J. B., Torring, T. & Gothelf, K. V. Site-selective conjugation of native proteins with DNA. Acc. Chem. Res. 50, 1367–1374 (2017).
Singh, Y., Murat, P. & Defrancq, E. Recent developments in oligonucleotide conjugation. Chem. Soc. Rev. 39, 2054–2070 (2010).
Chandrasekaran, A. R. & Rusling, D. A. Triplex-forming oligonucleotides: a third strand for DNA nanotechnology. Nucleic Acids Res. 46, 1021–1037 (2018).
Hollenstein, M. DNA catalysis: the chemical repertoire of DNAzymes. Molecules 20, 20777–20804 (2015).
Silverman, S. K. Catalytic DNA: scope, applications, and biochemistry of deoxyribozymes. Trends Biochem. Sci. 41, 595–609 (2016).
Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982).
Chen, J. H. & Seeman, N. C. Synthesis from DNA of a molecule with the connectivity of a cube. Nature 350, 631–633 (1991).
Winfree, E., Liu, F., Wenzler, L. A. & Seeman, N. C. Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998).
Paukstelis, P. J., Nowakowski, J., Birktoft, J. J. & Seeman, N. C. Crystal structure of a continuous three-dimensional DNA lattice. Chem. Biol. 11, 1119–1126 (2004).
Seeman, N. C. At the crossroads of chemistry, biology, and materials: structural DNA nanotechnology. Chem. Biol. 10, 1151–1159 (2003).
Yan, H., Park, S. H., Finkelstein, G., Reif, J. H. & LaBean, T. H. DNA-templated self-assembly of protein arrays and highly conductive nanowires. Science 301, 1882–1884 (2003).
Shih, W. M., Quispe, J. D. & Joyce, G. F. A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature 427, 618–621 (2004).
Rothemund, P. W. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).
Ke, Y. et al. Multilayer DNA origami packed on a square lattice. J. Am. Chem. Soc. 131, 15903–15908 (2009).
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).
Benson, E. et al. DNA rendering of polyhedral meshes at the nanoscale. Nature 523, 441–444 (2015).
Zhang, F. et al. Complex wireframe DNA origami nanostructures with multi-arm junction vertices. Nat. Nanotechnol. 10, 779–784 (2015).
Veneziano, R. et al. Designer nanoscale DNA assemblies programmed from the top down. Science 352, 1534 (2016).
Dietz, H., Douglas, S. M. & Shih, W. M. Folding DNA into twisted and curved nanoscale shapes. Science 325, 725–730 (2009).
Wagenbauer, K. F., Sigl, C. & Dietz, H. Gigadalton-scale shape-programmable DNA assemblies. Nature 552, 78–83 (2017).
Douglas, S. M. et al. Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res. 37, 5001–5006 (2009).
Kim, D. N., Kilchherr, F., Dietz, H. & Bathe, M. Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures. Nucleic Acids Res. 40, 2862–2868 (2012).
Castro, C. E. et al. A primer to scaffolded DNA origami. Nat. Methods 8, 221–229 (2011).
Snodin, B. E. K. et al. Introducing improved structural properties and salt dependence into a coarse-grained model of DNA. J. Chem. Phys. 142, 234901 (2015).
Maffeo, C., Yoo, J. & Aksimentiev, A. De novo reconstruction of DNA origami structures through atomistic molecular dynamics simulation. Nucleic Acids Res. 44, 3013–3019 (2016).
Sobczak, J. P., Martin, T. G., Gerling, T. & Dietz, H. Rapid folding of DNA into nanoscale shapes at constant temperature. Science 338, 1458–1461 (2012).
Stahl, E., Martin, T. G., Praetorius, F. & Dietz, H. Facile and scalable preparation of pure and dense DNA origami solutions. Angew. Chem. Int. Ed. Engl. 53, 12735–12740 (2014).
Wagenbauer, K. F. et al. How we make DNA origami. ChemBioChem 18, 1873–1885 (2017).
Shaw, A., Benson, E. & Hogberg, B. Purification of functionalized DNA origami nanostructures. ACS Nano 9, 4968–4975 (2015).
Douglas, S. M. et al. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 414–418 (2009).
Tikhomirov, G., Petersen, P. & Qian, L. Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns. Nature 552, 67–71 (2017).
Woo, S. & Rothemund, P. W. Programmable molecular recognition based on the geometry of DNA nanostructures. Nat. Chem. 3, 620–627 (2011).
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).
Han, D. et al. Single-stranded DNA and RNA origami. Science 358, eaao2648 (2017).
Geary, C., Rothemund, P. W. & Andersen, E. S. A single-stranded architecture for cotranscriptional folding of RNA nanostructures. Science 345, 799–804 (2014).
Praetorius, F. & Dietz, H. Self-assembly of genetically encoded DNA–protein hybrid nanoscale shapes. Science 355, eaam5488 (2017).
Ke, Y., Ong, L. L., Shih, W. M. & Yin, P. Three-dimensional structures self-assembled from DNA bricks. Science 338, 1177–1183 (2012).
Wei, B., Dai, M. & Yin, P. Complex shapes self-assembled from single-stranded DNA tiles. Nature 485, 623–626 (2012).
Yin, P. et al. Programming DNA tube circumferences. Science 321, 824–826 (2008).
Ong, L. L. et al. Programmable self-assembly of three-dimensional nanostructures from 10,000 unique components. Nature 552, 72–77 (2017).
Lin, C. et al. In vivo cloning of artificial DNA nanostructures. Proc. Natl Acad. Sci. USA 105, 17626–17631 (2008).
Kick, B., Praetorius, F., Dietz, H. & Weuster-Botz, D. Efficient production of single-stranded phage DNA as scaffolds for DNA origami. Nano Lett. 15, 4672–4676 (2015).
Engelhardt, F. A. S. et al. Custom-size, functional, and durable DNA origami with design-specific scaffolds. ACS Nano 13, 5015–5027 (2019).
Ducani, C., Kaul, C., Moche, M., Shih, W. M. & Hogberg, B. Enzymatic production of ‘monoclonal stoichiometric’ single-stranded DNA oligonucleotides. Nat. Methods 10, 647–652 (2013).
Schmidt, T. L. et al. Scalable amplification of strand subsets from chip-synthesized oligonucleotide libraries. Nat. Commun. 6, 8634 (2015).
Kishi, J. Y., Schaus, T. E., Gopalkrishnan, N., Xuan, F. & Yin, P. Programmable autonomous synthesis of single-stranded DNA. Nat. Chem. 10, 155–164 (2018).
Praetorius, F. et al. Biotechnological mass production of DNA origami. Nature 552, 84–87 (2017).
Gu, H., Furukawa, K., Weinberg, Z., Berenson, D. F. & Breaker, R. R. Small, highly active DNAs that hydrolyze DNA. J. Am. Chem. Soc. 135, 9121–9129 (2013).
Li, M. et al. In vivo production of RNA nanostructures via programmed folding of single-stranded RNAs. Nat. Commun. 9, 2196 (2018).
Elbaz, J., Yin, P. & Voigt, C. A. Genetic encoding of DNA nanostructures and their self-assembly in living bacteria. Nat. Commun. 7, 11179 (2016).
Chi, Q., Wang, G. & Jiang, J. The persistence length and length per base of single-stranded DNA obtained from fluorescence correlation spectroscopy measurements using mean field theory. Physica A 392, 1072–1079 (2013).
Rechendorff, K., Witz, G., Adamcik, J. & Dietler, G. Persistence length and scaling properties of single-stranded DNA adsorbed on modified graphite. J. Chem. Phys. 131, 095103 (2009).
Zhang, D. Y. & Winfree, E. Control of DNA strand displacement kinetics using toehold exchange. J. Am. Chem. Soc. 131, 17303–17314 (2009).
Andersen, E. S. et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459, 73–76 (2009).
Pan, J., Li, F., Cha, T. G., Chen, H. & Choi, J. H. Recent progress on DNA based walkers. Curr. Opin. Biotechnol. 34, 56–64 (2015).
Thubagere, A. J. et al. A cargo-sorting DNA robot. Science 357, eaan6558 (2017).
Gu, H., Chao, J., Xiao, S. J. & Seeman, N. C. A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205 (2010).
Valero, J., Pal, N., Dhakal, S., Walter, N. G. & Famulok, M. A bio-hybrid DNA rotor–stator nanoengine that moves along predefined tracks. Nat. Nanotechnol. 13, 496–503 (2018).
Han, D., Pal, S., Liu, Y. & Yan, H. Folding and cutting DNA into reconfigurable topological nanostructures. Nat. Nanotechnol. 5, 712–717 (2010).
Zhang, F., Nangreave, J., Liu, Y. & Yan, H. Reconfigurable DNA origami to generate quasifractal patterns. Nano Lett. 12, 3290–3295 (2012).
Wei, B., Ong, L. L., Chen, J., Jaffe, A. S. & Yin, P. Complex reconfiguration of DNA nanostructures. Angew. Chem. Int. Ed. Engl. 53, 7475–7479 (2014).
Choi, Y., Choi, H., Lee, A. C., Lee, H. & Kwon, S. A reconfigurable DNA accordion rack. Angew. Chem. Int. Ed. Engl. 57, 2811–2815 (2018).
Marras, A. E., Zhou, L., Su, H. J. & Castro, C. E. Programmable motion of DNA origami mechanisms. Proc. Natl Acad. Sci. USA 112, 713–718 (2015).
List, J., Falgenhauer, E., Kopperger, E., Pardatscher, G. & Simmel, F. C. Long-range movement of large mechanically interlocked DNA nanostructures. Nat. Commun. 7, 12414 (2016).
Ketterer, P., Willner, E. M. & Dietz, H. Nanoscale rotary apparatus formed from tight-fitting 3D DNA components. Sci. Adv. 2, e1501209 (2016).
Turek, V. A. et al. Thermo-responsive actuation of a DNA origami flexor. Adv. Funct. Mater. 28, 1706410 (2018).
Song, J. et al. Reconfiguration of DNA molecular arrays driven by information relay. Science 357, eaan3377 (2017).
Kopperger, E. et al. A self-assembled nanoscale robotic arm controlled by electric fields. Science 359, 296–301 (2018).
Maier, A. M. et al. Magnetic propulsion of microswimmers with DNA-based flagellar bundles. Nano Lett. 16, 906–910 (2016).
Kuzyk, A. et al. A light-driven three-dimensional plasmonic nanosystem that translates molecular motion into reversible chiroptical function. Nat. Commun. 7, 10591 (2016).
Yang, Y. et al. A photoregulated DNA-based rotary system and direct observation of its rotational movement. Chemistry 23, 3979–3985 (2017).
Liu, N. & Liedl, T. DNA-assembled advanced plasmonic architectures. Chem. Rev. 118, 3032–3053 (2018).
Zhou, C., Duan, X. & Liu, N. DNA-nanotechnology-enabled chiral plasmonics: from static to dynamic. Acc. Chem. Res. 50, 2906–2914 (2017).
Samanta, A., Banerjee, S. & Liu, Y. DNA nanotechnology for nanophotonic applications. Nanoscale 7, 2210–2220 (2015).
Lan, X. & Wang, Q. DNA-programmed self-assembly of photonic nanoarchitectures. NPG Asia Mater. 6, e97 (2014).
Zheng, J. et al. From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal. Nature 461, 74–77 (2009).
Simmons, C. R. et al. Construction and structure determination of a three-dimensional DNA crystal. J. Am. Chem. Soc. 138, 10047–10054 (2016).
Simmons, C. R. et al. Tuning the cavity size and chirality of self-assembling 3D DNA crystals. J. Am. Chem. Soc. 139, 11254–11260 (2017).
Stahl, E., Praetorius, F., de Oliveira Mann, C. C., Hopfner, K. P. & Dietz, H. Impact of heterogeneity and lattice bond strength on DNA triangle crystal growth. ACS Nano 10, 9156–9164 (2016).
McNeil, R. Jr. & Paukstelis, P. J. Core-shell and layer-by-layer assembly of 3D DNA crystals. Adv. Mater. 29, 1701019 (2017).
Zhang, T. et al. 3D DNA origami crystals. Adv. Mater. 30, e1800273 (2018).
Rinker, S. et al. nanostructures for distance-dependent multivalent ligand–protein binding. Nat. Nanotechnol. 3, 418–422 (2008).
Tokura, Y. et al. Fabrication of defined polydopamine nanostructures by DNA origami-templated polymerization. Angew. Chem. Int. Ed. Engl. 57, 1587–1591 (2018).
Kershner, R. J. et al. Placement and orientation of individual DNA shapes on lithographically patterned surfaces. Nat. Nanotechnol. 4, 557–561 (2009).
Hung, A. M. et al. Large-area spatially ordered arrays of gold nanoparticles directed by lithographically confined DNA origami. Nat. Nanotechnol. 5, 121–126 (2010).
Funke, J. J. & Dietz, H. Placing molecules with Bohr radius resolution using DNA origami. Nat. Nanotechnol. 11, 47–52 (2016).
Fu, J. et al. Assembly of multienzyme complexes on DNA nanostructures. Nat. Protoc. 11, 2243–2273 (2016).
Ke, G. et al. Directional regulation of enzyme pathways through the control of substrate channeling on a DNA origami scaffold. Angew. Chem. Int. Ed. Engl. 55, 7483–7486 (2016).
Zhang, Y., Tsitkov, S. & Hess, H. Proximity does not contribute to activity enhancement in the glucose oxidase-horseradish peroxidase cascade. Nat. Commun. 7, 13982 (2016).
Zhao, Z. et al. Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion. Nat. Commun. 7, 10619 (2016).
Sharonov, A. & Hochstrasser, R. M. Wide-field subdiffraction imaging by accumulated binding of diffusing probes. Proc. Natl Acad. Sci. USA 103, 18911–18916 (2006).
Jungmann, R. et al. Single-molecule kinetics and super-resolution microscopy by fluorescence imaging of transient binding on DNA origami. Nano Lett. 10, 4756–4761 (2010).
Dai, M., Jungmann, R. & Yin, P. Optical imaging of individual biomolecules in densely packed clusters. Nat. Nanotechnol. 11, 798–807 (2016).
Jungmann, R. et al. Quantitative super-resolution imaging with qPAINT. Nat. Methods 13, 439–442 (2016).
Zanacchi, F. C. et al. A DNA origami platform for quantifying protein copy number in super-resolution. Nat. Methods 14, 789–792 (2017).
Douglas, S. M., Bachelet, I. & Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831–834 (2012).
Bastings, M. M. C. et al. Modulation of the cellular uptake of DNA origami through control over mass and shape. Nano Lett. 18, 3557–3564 (2018).
Wang, P. et al. Visualization of the cellular uptake and trafficking of DNA origami nanostructures in cancer cells. J. Am. Chem. Soc. 140, 2478–2484 (2018).
Zhang, D. & Paukstelis, P. J. Enhancing DNA crystal durability through chemical crosslinking. Chem. Bio. Chem. 17, 1163–1170 (2016).
Gerling, T., Kube, M., Kick, B. & Dietz, H. Sequence-programmable covalent bonding of designed DNA assemblies. Sci. Adv. 4, eaau1157 (2018).
Zhao, J. et al. Post-assembly stabilization of rationally designed DNA crystals. Angew. Chem. Int. Ed. Engl. 54, 9936–9939 (2015).
Perrault, S. D. & Shih, W. M. Virus-inspired membrane encapsulation of DNA nanostructures to achieve in vivo stability. ACS Nano 8, 5132–5140 (2014).
Auvinen, H. et al. Protein coating of DNA nanostructures for enhanced stability and immunocompatibility. Adv. Healthc. Mater. 6, 1700692 (2017).
Agarwal, N. P., Matthies, M., Gur, F. N., Osada, K. & Schmidt, T. L. Block copolymer micellization as a protection strategy for DNA origami. Angew. Chem. Int. Ed. Engl. 56, 5460–5464 (2017).
Ponnuswamy, N. et al. Oligolysine-based coating protects DNA nanostructures from low-salt denaturation and nuclease degradation. Nat. Commun. 8, 15654 (2017).
Lee, A. J., Endo, M., Hobbs, J. K. & Walti, C. Direct single-molecule observation of mode and geometry of reca-mediated homology search. ACS Nano 12, 272–278 (2018).
Endo, M., Katsuda, Y., Hidaka, K. & Sugiyama, H. Regulation of DNA methylation using different tensions of double strands constructed in a defined DNA nanostructure. J. Am. Chem. Soc. 132, 1592–1597 (2010).
Nickels, P. C. et al. Molecular force spectroscopy with a DNA origami-based nanoscopic force clamp. Science 354, 305–307 (2016).
Funke, J. J. et al. Uncovering the forces between nucleosomes using DNA origami. Sci. Adv. 2, e1600974 (2016).
Kilchherr, F. et al. Single-molecule dissection of stacking forces in DNA. Science 353, eaaf5508 (2016).
Krishnan, S. et al. Molecular transport through large-diameter DNA nanopores. Nat. Commun. 7, 12787 (2016).
Langecker, M. et al. Synthetic lipid membrane channels formed by designed DNA nanostructures. Science 338, 932–936 (2012).
Ketterer, P. et al. DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex. Nat. Commun. 9, 902 (2018).
Fisher, P. D. E. et al. A programmable DNA origami platform for organizing intrinsically disordered nucleoporins within nanopore confinement. ACS Nano 12, 1508–1518 (2018).
Zhang, Z., Yang, Y., Pincet, F., Llaguno, M. C. & Lin, C. Placing and shaping liposomes with reconfigurable DNA nanocages. Nat. Chem. 9, 653–659 (2017).
Grome, M. W., Zhang, Z., Pincet, F. & Lin, C. Vesicle tubulation with self-assembling DNA nanosprings. Angew. Chem. Int. Ed. Engl. 57, 5330–5334 (2018).
Yang, Y. et al. Self-assembly of size-controlled liposomes on DNA nanotemplates. Nat. Chem. 8, 476–483 (2016).
Franquelim, H. G., Khmelinskaia, A., Sobczak, J. P., Dietz, H. & Schwille, P. Membrane sculpting by curved DNA origami scaffolds. Nat. Commun. 9, 811 (2018).
Ohmann, A. et al. A synthetic enzyme built from DNA flips 10(7) lipids per second in biological membranes. Nat. Commun. 9, 2426 (2018).
Akbari, E. et al. Engineering cell surface function with DNA origami. Adv. Mater. 29, 1703632 (2017).
Balzani, V., Credi, A. & Venturi, M. Light powered molecular machines. Chem. Soc. Rev. 38, 1542–1550 (2009).
Silvi, S., Venturi, M. & Credi, A. Light operated molecular machines. Chem. Commun. 47, 2483–2489 (2011).
Baker, D. What has de novo protein design taught us about protein folding and biophysics? Protein Sci. 28, 678–683 (2019).
Lin, Y.-R. et al. Control over overall shape and size in de novo designed proteins. Proc. Natl Acad. Sci. USA 112, E5478–E5485 (2015).
Chevalier, A. et al. Massively parallel de novo protein design for targeted therapeutics. Nature 550, 74 (2017).
Whitford, P. C. & Onuchic, J. N. What protein folding teaches us about biological function and molecular machines. Curr. Opin. Struct. Biol. 30, 57–62 (2015).
Giri Rao, V. V. H. & Gosavi, S. Using the folding landscapes of proteins to understand protein function. Curr. Opin. Struct. Biol. 36, 67–74 (2016).
Elber, R. & Kirmizialtin, S. Molecular machines. Curr. Opin. Struct. Biol. 23, 206–211 (2013).
Astumian, R. D. Microscopic reversibility as the organizing principle of molecular machines. Nat. Nanotechnol. 7, 684 (2012).
Cross, R. A. Mechanochemistry of the kinesin-1 ATPase. Biopolymer 105, 476–482 (2016).
Wang, W., Cao, L., Wang, C., Gigant, B. & Knossow, M. Kinesin, 30 years later: recent insights from structural studies. Protein Sci. 24, 1047–1056 (2015).
Sielaff, H., Yanagisawa, S., Frasch, W. D., Junge, W. & Börsch, M. Structural asymmetry and kinetic limping of single rotary F-ATP synthases. Molecules 24, 504 (2019).
Junge, W. & Nelson, N. ATP Synthase. Annu. Rev. Biochem. 84, 631–657 (2015).
Stewart, A. G., Laming, E. M., Sobti, M. & Stock, D. Rotary ATPases—dynamic molecular machines. Curr. Opin. Struct. Biol. 25, 40–48 (2014).
Watson, M. A. & Cockroft, S. L. Man-made molecular machines: membrane bound. Chem. Soc. Rev. 45, 6118–6129 (2016).
Kassem, S. et al. Artificial molecular motors. Chem. Soc. Rev. 46, 2592–2621 (2017).
Erbas-Cakmak, S., Leigh, D. A., McTernan, C. T. & Nussbaumer, A. L. Artificial molecular machines. Chem. Rev. 115, 10081–10206 (2015).
Baroncini, M. et al. Making and operating molecular machines: a multidisciplinary challenge. Chemistry Open 7, 169–179 (2018).
Astumian, R. D. & Hänggi, P. Brownian motors. Phys. Today, 33–39 (2002).
Dogan, M. Y. et al. Kinesin’s front head is gated by the backward orientation of its neck linker. Cell Rep. 10, 1967–1973 (2015).
Noji, H., Ueno, H. & McMillan, D. G. G. Catalytic robustness and torque generation of the F1-ATPase. Biophys. Rev. 9, 103–118 (2017).
The authors thank E. Feigl for making Figs. 1A and 1B. This work was financially supported by the Deutsche Forschungsgemeinschaft through the Gottfried-Wilhelm-Leibniz Program and by the European Commission through an ERC Consolidator Grant (#724261).
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
A process through which the disordered components of a system organize themselves into a defined ordered state. The process is guided by minimization of the free energy of the system. Protein folding is an example of molecular self-assembly.
- DNA nanotechnology
The design and self-assembly of DNA into pre-defined patterns and attempts to control the shapes and functions of the assembled nanostructures.
A class of mechanically interlocked molecules consisting of a ring entrapped between the two bulky ends of a dumbbell-shaped molecule.
A class of mechanically interlocked molecules comprising two or more interchained macrocyclic rings.
- Brownian motors
A molecule or a molecular system that converts random Brownian motion to directional motion at the nanoscale by doing work on the environment.
- DNA switches
Molecular switches made of DNA that transition between at least two distinct states using a trigger — for example, pH or metal ions.
- Persistence lengths
A physical parameter indicating the stiffness of a polymer such as DNA, defined as the length over which the molecule behaves like a rigid rod.
A DNA motif self-assembled from multiple single-stranded DNA oligomers to form a unit for further assembly of a nanostructure. There are usually one or more crossovers in each tile, rendering it more rigid.
- Sticky-ended DNA
A DNA partial duplex with a single-stranded overhang that can hybridize to another, complementary single-stranded overhang, thus ‘sticking’ the two partial duplexes together.
- DNA origamis
DNA nanostructures formed by folding a long single-stranded DNA scaffold via hybridization of many short DNA complements, known as staple strands.
The long single-stranded DNA template molecule, running through a whole DNA origami structure.
- DNA crossovers
The points at which a DNA single strand exits its hybridization axis and enters an adjacent helix to continue its hybridization in the second helical axis.
- Staple strands
The short DNA oligomers (usually 20–60 nucleotides long) used to staple different segments of the scaffold together and form a pre-determined geometry.
- Segment lengths
Distances between two consecutive crossovers, which are a multiple of 7 bp in a honeycomb packing and a multiple of 8 bp in a square packing.
- Wireframe tessellation
A DNA structure approximating a geometrical shape at its edges, through tiling of its surfaces by non-overlapping polygons that do not leave a gap.
- Click contacts
Topological surface features of a DNA nanostructure, in the forms of protrusions and recessions that are capable of forming base-stacking interactions between two shape-complementary features, thus binding them.
Also known as deoxyribozyme, DNA enzyme or catalytic DNA. A DNA oligonucleotide with a specific sequence that performs a chemical reaction similar to enzymes.
- Strand displacement reaction
(SDR). A hybridization scheme in which a longer complement (fuel strand) displaces a shorter complement (output strand) via branch migration to form a more stable duplex.
The unpaired segment of a partial DNA duplex, which can act as a seeding region to start a branch migration and a strand displacement reaction.
- DNA walkers
Small DNA oligonucleotides that can move on a molecular track by a series of hybridization–dehybridization cycles.
Originally an architectural concept; a particular type of structure that maintains its integrity through pervasive tensional forces. In a tensegrity, each individual structural element is under stress, but the overall structure is stable.
Oligonucleotides or small peptides that bind specifically to a target molecule.
- Ratchet effects
The mechanisms by which molecular motors use random thermal noise to produce directional motion.