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A single synthetic small molecule that generates force against a load


Some biomolecules are able to generate directional forces by rectifying random thermal motions. This allows these molecular machines to perform mechanical tasks such as intracellular cargo transport or muscle contraction1 in plants and animals. Although some artificial molecular machines have been synthesized2,3,4 and used collectively to perform mechanical tasks5,6,7, so far there have been no direct measurements of mechanical processes at the single-molecule level. Here we report measurements of the mechanical work performed by a synthetic molecule less than 5 nm long. We show that biased Brownian motion of the sub-molecular components in a hydrogen-bonded [2]rotaxane8—a molecular ring threaded onto a molecular axle—can be harnessed to generate significant directional forces. We used the cantilever of an atomic force microscope to apply a mechanical load to the ring during single-molecule pulling–relaxing cycles. The ring was pulled along the axle, away from the thermodynamically favoured binding site, and was then found to travel back to this site against an external load of 30 pN. Using fluctuation theorems, we were able to relate measurements of the work done at the level of individual rotaxane molecules to the free-energy change as previously determined from ensemble measurements. The results show that individual rotaxanes can generate directional forces of similar magnitude to those generated by natural molecular machines.

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Figure 1: Chemical structure of the rotaxane-based molecule shuttle.
Figure 2: Single-molecule force spectroscopy of the rotaxane.
Figure 3: Experimental AFM pulling curves.
Figure 4: Pulling–relaxing cycles for the rotaxane–PEO molecule.

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  1. Schliwa, M. (ed.) Molecular Motors (Wiley-VCH, 2003).

  2. Kinbara, K. & Aida, T. Toward intelligent molecular machines: directed motions of biological and artificial molecules and assemblies. Chem. Rev. 105, 1377–1400 (2005).

    Article  CAS  Google Scholar 

  3. Kay, E. R., Leigh, D. A. & Zerbetto, F. Synthetic molecular motors and mechanical machines. Angew. Chem. Int. Ed. 46, 72–191 (2007).

    Article  CAS  Google Scholar 

  4. Browne, W. & Feringa, B. L. Making molecular machines work. Nature Nanotech. 1, 25–35 (2006).

    Article  CAS  Google Scholar 

  5. Berná, J. et al. Macroscopic transport by synthetic molecular machines. Nature Mater. 4, 704–710 (2005).

    Article  Google Scholar 

  6. Liu, Y. et al. Linear artificial molecular muscles. J. Am. Chem. Soc. 127, 9745–9759 (2005).

    Article  CAS  Google Scholar 

  7. Eelkema, R. et al. Molecular machines: nanomotor rotates microscale objects. Nature 440, 163 (2006).

    Article  CAS  Google Scholar 

  8. Kay, E. R. & Leigh, D. A. Hydrogen bond-assembled synthetic molecular motors and machines. Top. Curr. Chem. 262, 133–177 (2005).

    Article  CAS  Google Scholar 

  9. Balzani, V. et al. Autonomous artificial nanomotor powered by sunlight. Proc. Natl Acad. Sci. USA 103, 1178–1183 (2006).

    Article  CAS  Google Scholar 

  10. Serreli, V., Lee, C-F., Kay, E. R. & Leigh, D. A. A molecular information ratchet. Nature 445, 523–527 (2007).

    Article  CAS  Google Scholar 

  11. Panman, M. R. et al. Operation mechanism of a molecular machine revealed using time-resolved vibrational spectroscopy. Science 328, 1255–1258 (2010).

    Article  CAS  Google Scholar 

  12. Rijs, A. M. et al. Controlled hydrogen-bond breaking in a rotaxane by discrete solvation. Angew. Chem. Int. Ed. 49, 3896–3900 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Special issue. Annu. Rev. Biochem. 77, 45–228 (2008).

  15. Evans, E. Probing the relation between force–lifetime–and chemistry in single molecular bonds. Annu. Rev. Biophys. Biomol. Struct. 30, 105–128 (2001).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  18. 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  CAS  Google Scholar 

  19. Hugel, T. et al. Single-molecule optomechanical cycle. Science 296, 1103–1106 (2002).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. Brough, B. et al. Evaluation of synthetic linear motor-molecule actuation energetics. Proc. Natl Acad. Sci. USA 103, 8583–8588 (2006).

    Article  CAS  Google Scholar 

  22. Altieri, A. et al. Remarkable positional discrimination in bistable light- and heat-switchable hydrogen-bonded molecular shuttles. Angew. Chem. Int. Ed. 42, 2296–2300 (2003).

    Article  CAS  Google Scholar 

  23. Rostovtsev, V. V., Green, L. G., Fokin, V. V. & Sharpless, K. B. A stepwise Huisgen cycloaddition process: copper(I)-catalysed regioselective ligation of azides and terminal alkynes. Angew. Chem. Int. Ed. 41, 2596–2599 (2002).

    Article  CAS  Google Scholar 

  24. Grandbois, M., Beyer, M., Rief, M., Clausen-Schaumann, H. & Gaub, H. E. How strong is a covalent bond? Science 283, 1727–1730 (1999).

    Article  CAS  Google Scholar 

  25. Duwez, A-S. et al. Mechanochemistry: targeted delivery of single molecules. Nature Nanotech. 1, 122–125 (2006).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Flory, P. J. Statistical Mechanics of Chain Molecules (Hanser, 1989).

  28. Mark, J. E. & Flory, P. J. The configuration of the polyoxyethylene chain. J. Am. Chem. Soc. 87, 1415–1423 (1965).

    Article  CAS  Google Scholar 

  29. Crooks, G. E. Entropy production fluctuation theorem and the nonequilibrium work relation for free-energy differences. Phys. Rev. E 60, 2721–2726 (1999).

    Article  CAS  Google Scholar 

  30. Liphardt, J., Dumont, S., Smith, S. B., Tinoco Jr, I. & Bustamante, C. Equilibrium information from nonequilibrium measurements in an experimental test of Jarzynski's equality. Science 296, 1832–1835 (2002).

    Article  CAS  Google Scholar 

  31. Collin, C. et al. Verification of the Crooks fluctuation theorem and recovery of RNA folding free energies. Nature 437, 231–234 (2005).

    Article  CAS  Google Scholar 

  32. Leigh, D. A., Wong, J. K. Y., Dehez, F. & Zerbetto, F. Unidirectional rotation in a mechanically interlocked molecular rotor. Nature 424, 174–179 (2003).

    Article  CAS  Google Scholar 

  33. Jarzynski, C. Nonequilibrium equality for free energy differences. Phys. Rev. Lett. 78, 2690–2693 (1997).

    Article  CAS  Google Scholar 

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This research was funded by the Fonds de la Recherche Scientifique-Fonds National pour la Recherche Scientifique (FRS-FRNS; Fonds de la Recherche Fondamentale Collective 2.4.512.07 and Mandat d'Impulsion Scientifique F.4.501.08 to A-S.D.), the Politique Scientifique Fédérale (BELSPO; IUAP VI/27), the European Research Council and the Engineering and Physical Sciences Research Council. C-A.F. is a Research Associate of the FRS-FNRS.

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P.L. and T.S-L. performed the AFM experiments and analysed the data. A.B. carried out the rotaxane synthesis and characterization studies. C-A.F. participated in rotaxane synthesis. A-S.D., C-A.F. and D.A.L. designed the experiments and prepared the manuscript.

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Correspondence to David A. Leigh or Anne-Sophie Duwez.

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The authors declare no competing financial interests.

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Lussis, P., Svaldo-Lanero, T., Bertocco, A. et al. A single synthetic small molecule that generates force against a load. Nature Nanotech 6, 553–557 (2011).

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