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Synthetic oligorotaxanes exert high forces when folding under mechanical load

Nature Nanotechnology volume 13, pages 209–213 (2018)Cite this article

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Abstract

Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3,4,5. Recently, combining the exquisite complexity of these two classes of molecules, donor–acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6,7,8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

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Fig. 1: Structure formula and co-conformation of the [5]rotaxane of the [0.5(n – 1) + 2] family.
Fig. 2: AFM-based mechanical unfolding of the [5]rotaxane in DMF.
Fig. 3: Pulling–relaxing cycles showing the reformation of one interaction under mechanical load.
Fig. 4: Pulling–relaxing experiments showing the numerous fluctuations between folded and unfolded states and determination of the force exerted by the molecule.

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References

  1. Guichard, G. & Huc, I. Synthetic foldamers. Chem. Commun. 47, 5933–5941 (2011).

    Article  Google Scholar 

  2. Le Bailly, B. A. F. & Clayden, J. Dynamic foldamer chemistry. Chem. Commun. 52, 4852–4863 (2016).

    Article  Google Scholar 

  3. Bruns, C. J. & Stoddart, J. F. The Nature of The Mechanical Bond: From Molecules to Machines (Wiley, Hoboken, NJ, 2017).

  4. Erbas-Cakmak, S., Leigh, D. A., McTernan, C. T. & Nussbaumer, A. L. Artificial molecular machines. Chem. Rev. 115, 10081–10206 (2015).

    Article  Google Scholar 

  5. Kay, E. R. & Leigh, D. A. Rise of the molecular machines. Angew. Chem. Int. Ed. 54, 10080–10088 (2015).

    Article  Google Scholar 

  6. Basu, S. et al. Donor–acceptor oligorotaxanes made to order. Chem. Eur. J. 17, 2107–2119 (2011).

    Article  Google Scholar 

  7. Zhu, Z. et al. Synthesis and solution-state dynamics of donor–acceptor oligorotaxane foldamers. Chem. Sci. 4, 1470–1483 (2013).

    Article  Google Scholar 

  8. Bruns, C. J. & Stoddart, J. F. Mechanically interlaced and interlocked donor–acceptor foldamers. Adv. Polym. Sci. 261, 271–294 (2013).

    Article  Google Scholar 

  9. Fisher, T. E., Marszalek, P. E. & Fernandez, J. M. Stretching single molecules into novel conformations using the atomic force microscope. Nat. Struct. Biol. 7, 719–724 (2000).

    Article  Google Scholar 

  10. Bustamante, C., Chemla, Y. R., Forde, N. R. & Izhaky, D. Mechanical processes in biochemistry. Annu. Rev. Biochem. 73, 705–748 (2004).

    Article  Google Scholar 

  11. Neuman, K. C. & Nagy, A. Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat. Methods 5, 491–505 (2008).

    Article  Google Scholar 

  12. Puchner, E. M. & Gaub, H. E. Force and function: probing proteins with AFM-based force spectroscopy. Curr. Opin. Struct. Biol. 19, 605–614 (2009).

    Article  Google Scholar 

  13. Liang, J. & Fernandez, J. M. Mechanochemistry: one bond at a time. ACS Nano 3, 1628–1645 (2009).

    Article  Google Scholar 

  14. Duwez, A.-S. & Willet, N. Molecular Manipulation with Atomic Force Microscopy (CRC Press, Boca Raton, 2012).

    Google Scholar 

  15. Hinterdorfer, P. & Dufrene, Y. F. Detection and localization of single molecular recognition events using atomic force microscopy. Nat. Methods 3, 347–355 (2006).

    Article  Google Scholar 

  16. Müller, D. J. & Dufrêne, Y. F. Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology. Nat. Nanotech. 3, 261–269 (2008).

    Article  Google Scholar 

  17. Janke, M. et al. A. Mechanically interlocked calix[4]arene dimers display reversible bond breakage under force. Nat. Nanotech. 4, 225–229 (2009).

    Article  Google Scholar 

  18. Lussis, P. et al. A single synthetic small molecule that generates force against a load. Nat. Nanotech. 6, 553–557 (2011).

    Article  Google Scholar 

  19. Van Quaethem, A., Lussis, P., Leigh, D. A., Duwez, A.-S. & Fustin, C.-A. Probing the mobility of catenane rings in single molecules. Chem. Sci. 5, 1449–1452 (2014).

    Article  Google Scholar 

  20. Odell, B. et al. Cyclobis(paraquat-p-phenylene). A tetracationic multipurpose receptor. Angew. Chem. Int. Ed. 27, 1547–1550 (1988).

    Article  Google Scholar 

  21. Zhu, Z. et al. Oligomeric pseudorotaxanes adopting infinite-chain lattice superstructures. Angew. Chem. Int. Ed. 51, 7231–7235 (2012).

    Article  Google Scholar 

  22. Franco, I., Schatz, G. C. & Ratner, M. A. Single-molecule pulling and the folding of donor–acceptor oligorotaxanes: phenomenology and interpretation. J. Chem. Phys. 131, 124902 (2009).

    Article  Google Scholar 

  23. Hunter, C. A. Quantifying intermolecular interactions: guidelines for the molecular recognition toolbox. Angew. Chem. Int. Ed. 43, 5310–5324 (2004).

    Article  Google Scholar 

  24. Beyer, M. K. & Clausen-Schaumann, H. Mechanochemistry: the mechanical activation of covalent bonds. Chem. Rev. 105, 2921–2948 (2005).

    Article  Google Scholar 

  25. Flory, P. J. Statistical mechanics of chain molecules. Br. Polym. J. 2, 302–303 (1989).

    Google Scholar 

  26. Lee, G. et al. Nanospring behaviour of ankyrin repeats. Nature 440, 246–249 (2006).

    Article  Google Scholar 

  27. Liphardt, J., Onoa, B., Smith, S. B., Tinoco, I. & Bustamante, C. Reversible unfolding of single RNA molecules by mechanical force. Science 292, 733–737 (2001).

    Article  Google Scholar 

  28. Cecconi, C., Shank, E., Bustamante, C. & Marqusee, S. Direct observation of the three-state folding of a single protein molecule. Science 309, 2057–2060 (2005).

    Article  Google Scholar 

  29. Junker, J. P. & Rief, M. Single-molecule force spectroscopy distinguishes target binding modes of calmodulin. Proc. Natl Acad. Sci. USA 106, 14361–14366 (2009).

    Article  Google Scholar 

  30. Junker, J. P., Ziegler, F. & Rief, M. Ligand-dependent equilibrium fluctuations of single calmodulin molecules. Science 323, 633–637 (2009).

    Article  Google Scholar 

  31. He, C. et al. Direct observation of the reversible two-state unfolding and refolding of an α/β protein by single-molecule atomic force microscopy. Angew. Chem. Int. Ed. 54, 9921–9925 (2015).

    Article  Google Scholar 

  32. Žoldák, G., Stigler, J., Pelz, B., Li, H. & Rief, M. Ultrafast folding kinetics and cooperativity of villin headpiece in single-molecule force spectroscopy. Proc. Natl Acad. Sci. USA 110, 18156–18161 (2013).

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Acknowledgements

D.S. thanks the Fonds de la Recherche Scientifique-Fonds National pour la Recherche Scientifique (FRS-FNRS) for his FRIA fellowship. The research was supported by the PDR T.0205.13 project of the FRS-FNRS at University of Liège and by the King Abdulaziz City of Science and Technology (KACST) as part of their Joint Center of Excellence in Integrated Nano-Systems (JCIN) at Northwestern University.

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Authors and Affiliations

  1. UR Molecular Systems, Department of Chemistry, University of Liège, Liège, Belgium

    Damien Sluysmans, Sandrine Hubert & Anne-Sophie Duwez

  2. Department of Chemistry, Northwestern University, Evanston, IL, USA

    Carson J. Bruns, Zhixue Zhu & J. Fraser Stoddart

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Contributions

D.S. and S.H. performed the AFM experiments and analysed the data. C.B. and Z.Z. carried out the oligorotaxane synthesis and characterization studies. A.-S.D. and J.F.S. designed the experiments. A.-S.D. and D.S. wrote the manuscript. All the authors discussed the results and commented on the manuscript.

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Correspondence to Anne-Sophie Duwez.

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Sluysmans, D., Hubert, S., Bruns, C.J. et al. Synthetic oligorotaxanes exert high forces when folding under mechanical load. Nature Nanotech 13, 209–213 (2018). https://doi.org/10.1038/s41565-017-0033-7

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