Article | Published:

Catalytic transport of molecular cargo using diffusive binding along a polymer track

Abstract

Transport at the molecular scale is a prerequisite for the development of future molecular factories. Here, we have designed oligoanionic molecular sliders on polycationic tracks that exploit Brownian motion and diffusive binding to transport cargo without using a chemical fuel. The presence of the polymer tracks increases the rate of bimolecular reactions between modified sliders by over two orders of magnitude. Molecular dynamics simulations showed that the sliders not only diffuse, but also jump and hop surprisingly efficiently along polymer tracks. Inspired by acetyl-coenzyme A transporting and delivering acetyl groups in many essential biochemical processes, we developed a new and unconventional type of catalytic transport involving sliders (including coenzyme A) picking up, transporting and selectively delivering molecular cargo. Furthermore, we show that the concept of diffusive binding can also be utilized for the spatially controlled transport of chemical groups across gels. This work represents a new concept for designing functional nanosystems based on random Brownian motion.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Data availability

The authors declare that all the data generated and analysed during this study are included within this Article and its Supplementary Information. The software and codes used to perform simulation and analysis are cited in the Article. The data sets are available from authors Y.H. and P.K. on reasonable request.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. 1.

    Shliwa, M. & Woehlke, G. Molecular motors. Nature 422, 759–765 (2003).

  2. 2.

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

  3. 3.

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

  4. 4.

    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).

  5. 5.

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

  6. 6.

    Grzybowski, B. A. & Huck, W. T. S. The nanotechnology of life-inspired systems. Nat. Nanotech. 11, 585–592 (2016).

  7. 7.

    Wickham, S. F. J. et al. Direct observation of stepwise movement of a synthetic molecular transporter. Nat. Nanotech. 6, 166–169 (2011).

  8. 8.

    Gu, H., Chao, J., Xiao, S. J. & Seeman, N. C. A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205 (2010).

  9. 9.

    von Delius, M., Geertsema, E. M. & Leigh, D. A. A synthetic small molecule that can walk down a track. Nat. Chem. 2, 96–101 (2010).

  10. 10.

    Kassem, S., Lee, A. T. L., Leigh, D. A., Markevicius, A. & Solà, J. Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm. Nat. Chem. 8, 138–143 (2016).

  11. 11.

    Chen, J., Wezenberg, S. J. & Feringa, B. L. Intramolecular transport of small-molecule cargo in a nanoscale device operated by light. Chem. Commun. 52, 6765–6768 (2016).

  12. 12.

    Soh, S., Byrska, M., Kandere-Grzybowska, K. & Grzybowski, B. A. Reaction–diffusion systems in intracellular molecular transport and control. Angew. Chem. Int. Ed. 49, 4170–4198 (2010).

  13. 13.

    Kopperger, E., Pirzer, T. & Simmel, F. C. Diffusive transport of molecular cargo tethered to a DNA origami platform. Nano Lett. 15, 2693–2699 (2015).

  14. 14.

    Thubagere, A. J. et al. A cargo-sorting DNA robot. Science 357, 1112–1121 (2017).

  15. 15.

    Perl, A. et al. Gradient-driven motion of multivalent ligand molecules along a surface functionalized with multiple receptors. Nat. Chem. 3, 317–322 (2011).

  16. 16.

    Pulcu, G. S., Mikhailova, E., Choi, L. S. & Bayley, H. Continuous observation of the stochastic motion of an individual small-molecule walker. Nat. Nanotech. 10, 76–83 (2015).

  17. 17.

    Campaña, A. G. et al. A small molecule that walks non-directionally along a track without external intervention. Angew. Chem. Int. Ed. 51, 5480–5483 (2012).

  18. 18.

    Campaña, A. G., Leigh, D. A. & Lewandowska, U. One-dimensional random walk of a synthetic small molecule toward a thermodynamic sink. J. Am. Chem. Soc. 135, 8639–8645 (2013).

  19. 19.

    Thordarson, P., Bijsterveld, E. J. A., Rowan, A. E. & Nolte, R. J. M. Epoxidation of polybutadiene by a topologically linked catalyst. Nature 424, 915–918 (2003).

  20. 20.

    van Dongen, S. F. M. et al. A clamp-like biohybrid catalyst for DNA oxidation. Nat. Chem. 5, 945–951 (2013).

  21. 21.

    Givaty, O. & Levy, Y. Protein sliding along DNA: dynamics and structural characterization. J. Mol. Biol. 385, 1087–1097 (2009).

  22. 22.

    Vuzman, D. & Levy, Y. DNA search efficiency is modulated by charge composition and distribution in the intrinsically disordered tail. Proc. Natl Acad. Sci. USA 107, 21004–21009 (2010).

  23. 23.

    Blainey, P. C. et al. Nonspecifically bound proteins spin while diffusing along DNA. Nat. Struct. Mol. Biol. 16, 1224–1229 (2009).

  24. 24.

    Mangel, W. F. et al. Molecular sled is an eleven-amino acid vehicle facilitating biochemical interactions via sliding components along DNA. Nat. Commun. 7, 10202 (2016).

  25. 25.

    Berg, O. G., Winter, R. B. & von Hippel, P. H. Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory. Biochemistry 20, 6929–6948 (1981).

  26. 26.

    Zhong, D., Douhal, A. & Zewail, A. H. Femtosecond studies of protein–ligand hydrophobic binding and dynamics: human serum albumin. Proc. Natl Acad. Sci. USA 97, 14056–14061 (2000).

  27. 27.

    Jeltsch, A. & Urbanke, C. in Restriction Endonucleases (ed. Pingoud, A. M.) 95–110 (Nucleic Acids and Molecular Biology series, Springer, Heidelberg, 2004).

  28. 28.

    Ross, P. D. & Subramanian, S. Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20, 3096–3102 (1981).

  29. 29.

    Turkin, A. et al. Speeding up biomolecular interactions by molecular sledding. Chem. Sci. 7, 916–920 (2016).

  30. 30.

    Xiong, K., Erwin, G. S., Ansari, A. Z. & Blainey, P. C. Sliding on DNA: from peptides to small molecules. Angew. Chem. Int. Ed. 55, 15110–15114 (2016).

  31. 31.

    Zhang, L. et al. Accelerating chemical reactions by molecular sledding. Chem. Commun. 53, 6331–6334 (2017).

  32. 32.

    Zhang, D., Gullingsrud, J. & McCammon, J. A. Potentials of mean force for acetylcholine unbinding from the α7 nicotinic acetylcholine receptor ligand-binding domain. J. Am. Chem. Soc. 128, 3019–3026 (2006).

  33. 33.

    Giorgino, T. Computing Diffusion Coefficients in Macromolecular Simulations: The Diffusion Coefficient Tool for VMD https://github.com/tonigi/vmd_diffusion_coefficient (2011).

  34. 34.

    Elovson, J. & Vagelos, P. R. Acyl carrier protein. X. Acyl carrier protein synthetase. J. Biol. Chem. 243, 3603–3611 (1968).

  35. 35.

    Fang, X., Yu, P. & Morandi, B. Catalytic reversible alkene-nitrile interconversion through controllable transfer hydrocyanation. Science 351, 832–836 (2016).

  36. 36.

    Fang, X., Cacherat, B. & Morandi, B. CO- and HCl-free synthesis of acid chlorides from unsaturated hydrocarbons via shuttle catalysis. Nat. Chem. 9, 1105–1109 (2017).

  37. 37.

    Maiti, S., Fortunati, I., Ferrante, C., Scrimin, P. & Prins, L. J. Dissipative self-assembly of vesicular nanoreactors. Nat. Chem. 8, 725–731 (2016).

  38. 38.

    Campbell, C. J., Klajn, R., Fialkowski, M. & Grzybowski, B. A. One-step multilevel microfabrication by reaction–diffusion. Langmuir 21, 418–423 (2005).

  39. 39.

    Semenov, S. N., Markvoort, A. J., de Greef, T. F. A. & Huck, W. T. S. Threshold sensing through a synthetic enzymatic reaction–diffusion network. Angew. Chem. Int. Ed. 53, 8066–8069 (2014).

  40. 40.

    Bochicchio, D., Salvalaglio, M. & Pavan, G. M. Into the dynamics of supramolecular polymers at submolecular resolution. Nat. Commun. 8, 147 (2017).

Download references

Acknowledgements

This work was supported by the Netherlands Organization for Scientific Research (NWO) TOPPUNT grant 718.014.001 (to W.T.S.H.), the Ministry of Education, Culture and Science (Gravity programme, 024.001.035, to W.T.S.H.), an NSF DMR-1506886 grant (to P.K.) and by start-up funding from the University of Texas at El Paso (to L.V.). H.Z. is a recipient of a Radboud Excellence Fellowship.

Author information

W.T.S.H. supervised the research. L.Z., H.Z. and W.T.S.H. planned the project and designed experiments. L.Z. and H.Z. synthesized and characterized all compounds. L.Z. and H.Z. performed kinetic studies of fluorogenic reactions and analysed data. L.Z. and H.Q. performed catalytic molecular transfer experiments and analysed data. L.Z. and J.M. analysed the ITC data. Y.H., L.V. and P.K. performed computational simulations. L.Z., Y.H., P.K. and W.T.S.H. wrote the manuscript.

Competing interests

The authors declare no competing interests.

Correspondence to Lifei Zheng or Wilhelm T. S. Huck.

Supplementary information

Supplementary Information

Experimental procedures, characterization of all compounds, and details of molecular dynamic simulations.

Supplementary Movie 1

Supplementary movie showing diffusion of Arg18-S-coumarin inside nc-PAAm gel matrix.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark
Fig. 1: Schematic representation of the slider–track system.
Fig. 2: Kinetics studies of fluorogenic reactions between chemically charged sliders.
Fig. 3: MD simulations of sliders on polycationic tracks.
Fig. 4: Inter-track molecular cargo transport.
Fig. 5: Molecular cargo transport within physically separated compartments.