Abstract
DNA nanotechnology has emerged as a powerful tool to precisely design and control molecular circuits, machines and nanostructures. A major goal in this field is to build devices with life-like properties, such as directional motion, transport, communication and adaptation. Here we provide an overview of the nascent field of dissipative DNA nanotechnology, which aims at developing life-like systems by combining programmable nucleic-acid reactions with energy-dissipating processes. We first delineate the notions, terminology and characteristic features of dissipative DNA-based systems and then we survey DNA-based circuits, devices and materials whose functions are controlled by chemical fuels. We emphasize how energy consumption enables these systems to perform work and cyclical tasks, in contrast with DNA devices that operate without dissipative processes. The ability to take advantage of chemical fuel molecules brings dissipative DNA systems closer to the active molecular devices that exist in nature.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Seeman, N. C. & Sleiman, H. F. DNA nanotechnology. Nat. Rev. Mater. 3, 17068 (2017).
Harroun, S. G. et al. Programmable DNA switches and their applications. Nanoscale 10, 4607–4641 (2018).
Simmel, F. C., Yurke, B. & Singh, H. R. Principles and applications of nucleic acid strand displacement reactions. Chem. Rev. 119, 6326–6369 (2019).
Ye, D., Zuo, X. & Fan, C. DNA nanotechnology-enabled interfacial engineering for biosensor development. Annu. Rev. Anal. Chem. 11, 171–195 (2018).
Li, J., Green, A. A., Yan, H. & Fan, C. Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation. Nat. Chem. 9, 1056–1067 (2017).
Shin, J. –S. & Pierce, N. A. A synthetic DNA walker for molecular transport. J. Am. Chem. Soc. 126, 10834–10835 (2004).
Hu, Q., Li, H., Wang, L., Gu, H. & Fan, C. DNA nanotechnology-enabled drug delivery systems. Chem. Rev. 119, 6459–6506 (2019).
Kim, T., Nam, K., Kim, Y. M., Yang, K. & Roh, Y. H. DNA-assisted smart nanocarriers: progress, challenges and opportunities. ACS Nano 15, 1942–1951 (2021).
Wang, F., Lu, C. –H. & Willner, I. From cascaded catalytic nucleic acids to enzyme-DNA nanostructures: controlling reactivity, sensing, logic operations, and assembly of complex structures. Chem. Rev. 114, 2881–2941 (2014).
Göpfrich, K., Platzman, I. & Spatz, J. P. Mastering complexity: towards bottom-up construction of multifunctional eukaryotic synthetic cells. Trends Biotechnol. 36, 938–951 (2018).
Zhang, D. Y. & Seelig, G. Dynamic DNA nanotechnology using strand-displacement reactions. Nat. Chem. 3, 103–113 (2011).
Walsh, C. T., Tu, B. P. & Tang, Y. Eight kinetically stable but thermodynamically activated molecules that power cell metabolism. Chem. Rev. 118, 1460–1494 (2018).
Astumian, R. D. Thermodynamics and kinetics of molecular motors. Biophys. J. 98, 2401–2409 (2010).
Ananthakrishnan, R. & Ehrlicher, A. The forces behind cell movement. Int. J. Biol. Sci. 3, 303–317 (2007).
Schliwa, M. & Woehlke, G. Molecular motors. Nature 422, 759–765 (2003).
Zhang, D. Y. & Winfree, E. Control of DNA strand displacement kinetics using toehold exchange. J. Am. Chem. Soc. 131, 17303–17314 (2009).
Seelig, G., Soloveichik, D., Zhang, D. Y. & Winfree, E. Enzyme-free nucleic acid logic circuits. Science 314, 1585–1588 (2006).
Zhang, D. Y., Hariadi, R. F., Choi, H. M. T. & Winfree, E. Integrating DNA strand-displacement circuitry with DNA tile self-assembly. Nat. Commun. 4, 1965 (2013).
Green, L. N., Amodio, A., Subramanian, H. K. K. S., Ricci, F. & Franco, E. pH-driven reversible self-assembly of micron-scale DNA scaffolds. Nano Lett. 17, 7283–7288 (2017).
Amodio, A., Del Grosso, E., Troina, A., Placidi, E. & Ricci, F. Remote electronic control of DNA-based reactions and nanostructures assembly. Nano Lett. 18, 2918–2923 (2018).
Amodio, A., Adedeji, A. F., Castronovo, M., Franco, E. & Ricci, F. pH-controlled assembly of DNA tiles. J. Am. Chem. Soc. 138, 12735–12738 (2016).
Ranallo, S., Sorrentino, D. & Ricci, F. Orthogonal regulation of DNA nanostructure self-assembly and disassembly using antibodies. Nat. Commun. 10, 5509 (2019).
Yurke, B., Turberfield, A. J., Mills, A. P., Simmel, F. C. & Neumann, J. L. A DNA-fuelled molecular machine made of DNA. Nature 406, 605–608 (2000).
Das, J., Gabrielli, L. & Prins, L. J. Chemically-fueled self-assembly in biology and chemistry. Angew. Chem. Int. Ed. 60, 20120–20143 (2021).
Aprahamian, I. The future of molecular machines. ACS Cent. Sci. 6, 347–358 (2020).
Astumian, R. D. How molecular motors work - insights from the molecular machinist’s toolbox: the Nobel prize in Chemistry 2016. Chem. Sci. 8, 840–845 (2017).
Ragazzon, G. & Prins, L. J. Energy consumption in chemical fuel-driven self-assembly. Nat. Nanotechnol. 13, 882–889 (2018).
Astumian, R. D. Kinetic asymmetry allows macromolecular catalysts to drive an information ratchet. Nat. Commun. 10, 3837 (2019).
Feng, Y. et al. Molecular pumps and motors. J. Am. Chem. Soc. 143, 5569–5591 (2021).
Novák, B. & Tyson, J. J. Design principles of biochemical oscillators. Nat. Rev. Mol. Cell Biol. 9, 981–991 (2008).
Elowitz, M. B. & Leibler, S. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335–338 (2000).
Gardner, T. S., Cantor, C. R. & Collins, J. J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000).
Kim, J., White, K. S. & Winfree, E. Construction of an in vitro bistable circuit from synthetic transcriptional switches. Mol. Syst. Biol. 2, 68 (2006).
Kim, J. & Winfree, E. Synthetic in vitro transcriptional oscillators. Mol. Syst. Biol. 7, 465 (2011).
Subsoontorn, P., Kim, J. & Winfree, E. Ensemble bayesian analysis of bistability in a synthetic transcriptional switch. ACS Synth. Biol. 1, 299–316 (2012).
Schaffter, S. W. & Schulman, R. Building in vitro transcriptional regulatory networks by successively integrating multiple functional circuit modules. Nat. Chem. 11, 829–838 (2019).
Franco, E. et al. Timing molecular motion and production with a synthetic transcriptional clock. Proc. Natl Acad. Sci USA 108, E784–E793 (2011).
Weitz, M. et al. Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator. Nat. Chem. 6, 295–302 (2014).
Dupin, A. & Simmel, F. C. Signalling and differentiation in emulsion-based multi-compartmentalized in vitro gene circuits. Nat. Chem. 11, 32–39 (2019).
Padirac, A., Fujii, T. & Rondelez, Y. Bottom-up construction of in vitro switchable memories. Proc. Natl Acad. Sci. USA 109, E3212–E3220 (2012).
Montagne, K., Plasson, R., Sakai, Y., Fujii, T. & Rondelez, Y. Programming an in vitro DNA oscillator using a molecular networking strategy. Mol. Syst. Biol. 7, 466 (2011).
Fujii, T. & Rondelez, Y. Predator–prey molecular ecosystems. ACS Nano 7, 27–34 (2013).
Lotka, A. Undamped oscillations derived from the law of mass action. J. Am. Chem. Soc. 42, 1595–1599 (1920).
Volterra, V. Fluctuations in the abundance of a species considered mathematically. Nature 118, 558–560 (1926).
Zadorin, A. S. et al. Synthesis and materialization of a reaction-diffusion French flag pattern. Nat. Chem. 9, 990–996 (2017).
Gines, G. et al. Microscopic agents programmed by DNA circuits. Nat. Nanotechnol. 12, 351–359 (2017).
Der Hofstadt, M. V., Galas, J. –C. & Estevez-Torres, A. Spatiotemporal patterning of living cells with extracellular DNA programs. ACS Nano 15, 1741–1752 (2021).
Deng, J. & Walther, A. Fuel-driven transient DNA strand displacement circuitry with self-resetting function. J. Am. Chem. Soc. 142, 21102–21109 (2020).
Wang, S., Yue, L., Wulf, V., Lilienthal, S. & Willner, I. Dissipative constitutional dynamic networks for tunable transient responses and catalytic functions. J. Am. Chem. Soc. 142, 17480–17488 (2020).
Zhou, Z., Ouyang, Y., Wang, J. & Willner, I. Dissipative gated and cascaded DNA networks. J. Am. Chem. Soc. 143, 5071–5079 (2021).
Srinivas, N., Parkin, J., Seelig, G., Winfree, E. & Soloveichik, D. Enzyme-free nucleic acid dynamical systems. Science 358, eaal2052 (2017).
Hirokawa, N. & Noda, Y. Intracellular transport and kinesin superfamily proteins, KIFs: structure, function and dynamics. Physiol. Rev. 88, 1089–1118 (2008).
Gennerich, A. & Vale, R. D. Walking the walk: how kinesin and dynein coordinate their steps. Curr. Opin. Cell Biol. 21, 59–67 (2009).
Bath, J., Green, S., Allen, K. & Turberfield, A. Mechanism for a directional, processive and reversible DNA motor. Small 5, 1513–1516 (2009).
Sherman, W. B. & Seeman, N. C. A precisely controlled DNA biped walking device. Nano Lett. 4, 1204–1207 (2004).
Yin, P., Choi, H. M. T., Calvert, C. R. & Pierce, N. A. Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008).
Omabegho, T., Sha, R. & Seeman, N. C. A bipedal DNA Brownian motor with coordinated legs. Science 324, 67–71 (2009).
Muscat, R. A., Bath, J. & Turberfield, A. J. A programmable molecular robot. Nano Lett. 11, 982–987 (2011).
Thubagere, A. J. et al. A cargo-sorting DNA robot. Science 357, eaan6558 (2017).
Green, S. J., Bath, J. & Turberfield, A. J. Coordinated chemomechanical cycles: a mechanism for autonomous molecular motion. Phys. Rev. Lett. 101, 238101 (2008).
Yin, P., Yan, H., Daniell, X. G., Turberfield, A. J. & Reif, J. H. A unidirectional DNA walker that moves autonomously along a track. Angew. Chem. Int. Ed. 43, 4906–4911 (2004).
Bath, J., Green, S. J. & Turberfield, A. J. A free-running DNA motor powered by a nicking enzyme. Angew. Chem. Int. Ed. 44, 4358–4361 (2005).
Lund, K. et al. Molecular robots guided by prescriptive landscapes. Nature 465, 206–210 (2010).
Wickham, S. F. J. et al. Direct observation of stepwise movement of a synthetic molecular transporter. Nat. Nanotechnol. 6, 166–169 (2011).
Wickham, S. F. J. et al. A DNA-based molecular motor that can navigate a network of tracks. Nat. Nanotechnol. 7, 169–173 (2012).
Tian, Y., He, Y., Chen, Y., Yin, P. & Mao, C. A DNAzyme that walks processively and autonomously along a one-dimensional track. Angew. Chem. Int. Ed. 44, 4355–4358 (2005).
Vallée-Bélisle, A., Ricci, F. & Plaxco, K. W. Thermodynamic basis for the optimization of binding-induced biomolecular switches and structure-switching biosensors. Proc. Natl Acad. Sci. USA 106, 13802–13807 (2009).
Chen, Y., Wang, M. & Mao, C. An autonomous DNA nanomotor powered by a DNA enzyme. Angew. Chem. Int. Ed. 43, 3554–3557 (2004).
Safdar, S., Lammertyn, J. & Spasic, D. RNA-cleaving NAzymes: the next big thing in biosensing? Trends Biotechnol. 38, 1343–1359 (2020).
Bishop, J. D. & Klavins, E. An improved autonomous DNA nanomotor. Nano Lett. 7, 2574–2577 (2007).
Porchetta, A., Idili, A., Vallée-Bélisle, A. & Ricci, F. A general strategy to introduce pH-induced allostery in DNA-based receptors to achieve controlled release of ligands. Nano Lett. 15, 4467–4471 (2015).
Del Grosso, E., Amodio, A., Ragazzon, G., Prins, L. & Ricci, F. Dissipative synthetic DNA-based receptors for the transient load and release of molecular cargo. Angew. Chem. Int. Ed. 57, 10489–10493 (2018).
Idili, A., Plaxco, K. W., Vallée-Bélisle, A. & Ricci, F. Thermodynamic basis for engineering high-affinity, high-specificity binding-induced DNA clamp nanoswitches. ACS Nano 7, 10863–10869 (2013).
Rangel, A. E., Hariri, A. A., Eisenstein, M. & Soh, H. T. Engineering aptamer switches for multifunctional stimulus-responsive nanosystems. Adv. Mater. 32, e2003704 (2020).
Del Grosso, E., Ragazzon, G., Prins, L. & Ricci, F. Fuel‐responsive allosteric DNA‐based aptamers for the transient release of ATP and cocaine. Angew. Chem. Int. Ed. 58, 5582–5586 (2019).
Liedl, T. & Simmel, F. C. Switching the conformation of a DNA molecule with a chemical oscillator. Nano Lett. 5, 1894–1898 (2005).
Gehring, K., Leroy, J. L. & Guéron, M. A tetrameric DNA structure with protonated cytosine.cytosine base pairs. Nature 363, 561–565 (1993).
Liu, D. & Balasubramanian, S. A proton-fuelled DNA nanomachine. Angew. Chem. Int. Ed. 42, 5734–5736 (2003).
Heinen, L. & Walther, A. Temporal control of i-motif switch lifetimes for autonomous operation of transient DNA nanostructures. Chem. Sci. 8, 4100–4107 (2017).
Mariottini, D., Del Giudice, D., Ercolani, G., Di Stefano, S. & Ricci, F. Dissipative operation of pH-responsive DNA-based nanodevices. Chem. Sci. 12, 11735–11739 (2021).
Heinen, L., Heuser, T., Steinschulte, A. & Walther, A. Antagonistic enzymes in a biocatalytic pH feedback system program autonomous DNA hydrogel life cycles. Nano Lett. 17, 4989–4995 (2017).
Del Grosso, E., Ponzo, I., Ragazzon, G., Prins, L. J. & Ricci, F. Disulfide-linked allosteric modulators for multi-cycle kinetic control of DNA-based nanodevices. Angew. Chem. Int. Ed. 59, 21058–21063 (2020).
Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).
Douglas, S. M. et al. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 414–418 (2009).
Ijäs, H., Nummelin, S., Shen, B., Kostiainen, M. A. & Linko, V. Dynamic DNA origami devices: from strand-displacement reactions to external-stimuli responsive systems. Int. J. Mol. Sci. 19, 2114 (2018).
Turek, V. A. et al. Thermo-responsive actuation of a DNA origami flexor. Adv. Funct. Mater. 28, 1706410 (2018).
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).
Rothemund, P. W. K. et al. Design and characterization of programmable DNA nanotubes. J. Am. Chem. Soc. 126, 16344–16352 (2004).
Agarwal, S. & Franco, E. Enzyme-driven assembly and disassembly of hybrid DNA-RNA nanotubes. J. Am. Chem. Soc. 141, 7831–7841 (2019).
Green, L. N. et al. Autonomous dynamic control of DNA nanostructure self-assembly. Nat. Chem. 11, 510–520 (2019).
Gentile, S. et al. Spontaneous reorganization of DNA-based polymers in higher ordered structures fueled by RNA. J. Am. Chem. Soc. 143, 20296–20301 (2021).
Del Grosso, E., Prins, L. J. & Ricci, F. Transient DNA-based nanostructures controlled by redox inputs. Angew. Chem. Int. Ed. 59, 13238–13245 (2020).
Deng, J. & Walther, A. Pathway complexity in fuel-driven DNA nanostructures with autonomous reconfiguration of multiple dynamic steady states. J. Am. Chem. Soc. 142, 685–689 (2020).
Deng, J. & Walther, A. ATP-responsive and ATP-fueled self-assembling systems and materials. Adv. Mater. 32, e2002629 (2020).
Heinen, L. & Walther, A. Programmable dynamic steady states in ATP-driven nonequilibrium DNA systems. Sci. Adv. 5, eaaw0590 (2019).
Deng, J., Bezold, D., Jessen, H. J. & Walther, A. Multiple light control mechanisms in ATP-fueled non-equilibrium DNA systems. Angew. Chem. Int. Ed. 59, 12084–12092 (2020).
Deng, J. & Walther, A. Programmable ATP-fueled DNA coacervates by transient liquid-liquid phase separation. Chem 6, 3329–3343 (2020).
Deng, J., Liu, W., Sun, M. & Walther, A. Dissipative organization of DNA oligomers for transient catalytic function. Angew. Chem. Int. Ed. 61, e202113477 (2022).
Deng, J. & Walther, A. Autonomous DNA nanostructures instructed by hierarchically concatenated chemical reaction networks. Nat. Commun. 12, 5132 (2021).
Deng, J. & Walther, A. ATP-powered molecular recognition to engineer transient multivalency and self-sorting 4D hierarchical systems. Nat. Commun. 11, 3658 (2020).
Rizzuto, F. J. et al. A dissipative pathway for the structural evolution of DNA fibres. Nat. Chem. 13, 843–849 (2021).
Li, N. et al. Self-resetting molecular probes for nucleic acids detection enabled by fuel dissipative systems. Nano Today 41, 101308 (2021).
Ouyang, Y., Zhang, P., Manis-Levy, H., Paltiel, Y. & Willner, I. Transient dissipative optical properties of aggregated Au nanoparticles, CdSe/ZnS quantum dots, and supramolecular nucleic acid-stabilized Ag nanoclusters. J. Am. Chem. Soc. 143, 17622–17632 (2021).
Hamada, S. et al. Dynamic DNA material with emergent locomotion behavior powered by artificial metabolism. Sci. Robot. 4, eaaw3512 (2019).
Della Sala, F., Neri, S., Maiti, S., Chen, J. L. –Y. & Prins, L. J. Transient self-assembly of molecular nanostructures driven by chemical fuels. Curr. Opin. Biotechnol. 46, 27–33 (2017).
Rieß, B., Grötsch, R. K. & Boekhoven, J. The design of dissipative molecular assemblies driven by chemical reaction cycles. Chem. 6, 552–578 (2020).
Lavickova, B., Laohakunakorn, N. & Maerkl, S. J. A partially self-regenerating synthetic cell. Nat. Commun. 11, 6340 (2020).
Zhang, Y., Chan, P. P. Y. & Herr, A. E. Rapid capture and release of nucleic acids through a reversible photo-cycloaddition reaction in a psoralen-functionalized hydrogel. Angew. Chem. Int. Ed. 57, 2357–2361 (2018).
Dorsey, P. J., Rubanov, M., Wang, W. & Schulman, R. Digital maskless photolithographic patterning of DNA-functionalized pfoly(ethylene glycol) diacrylate hydrogels with visible light enabling photodirected release of oligonucleotides. ACS Macro Lett. 8, 1133–1140 (2019).
Kay, E. R., Leigh, D. A. & Zerbetto, F. Synthetic molecular motors and mechanical machines. Angew. Chem. Int. Ed. 46, 72–191 (2007).
Astumian, R. D. Microscopic reversibility as the organizing principle of molecular machines. Nat. Nanotechnol. 7, 684–688 (2012).
Amano, S., Borsley, S., Leigh, D. A. & Sun, Z. Chemical engines: driving systems away from equilibrium through catalyst reaction cycles. Nat. Nanotechnol. 16, 1057–1067 (2021).
Desai, A. & Mitchison, T. J. Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol. 13, 83–117 (1997).
Wang, C. et al. Gated dissipative dynamic artificial photosynthetic model systems. J. Am. Chem. Soc. 143, 12120–12218 (2021).
Wang, J. et al. DNAzyme- and light-induced dissipative and gated DNA networks. Chem. Sci. 12, 11204–11212 (2021).
Del Grosso, E. et al. Dissipative control over the toehold-mediated DNA strand displacement reaction. Angew. Chem. Int. Ed. 61, e202201929 (2022).
Acknowledgements
F.R. is thankful for support from the European Research Council (ERC Consolidator Grant project no. 819160) and Associazione Italiana per la Ricerca sul Cancro, AIRC (project no. 21965). L.J.P. acknowledges the Italian Ministry of Education and Research (grant no. 2017E44A9P). E.F. acknowledges financial support by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under award no. DE-SC-0010595.
Author information
Authors and Affiliations
Contributions
E.D.G., E.F., L.J.P. and F.R. contributed to discussions and wrote the manuscript.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Peer review
Peer review information
Nature Chemistry thanks Chunhai Fan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Del Grosso, E., Franco, E., Prins, L.J. et al. Dissipative DNA nanotechnology. Nat. Chem. 14, 600–613 (2022). https://doi.org/10.1038/s41557-022-00957-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41557-022-00957-6