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Gradient-driven motion of multivalent ligand molecules along a surface functionalized with multiple receptors

Abstract

The kinetics of multivalent (multisite) interactions at interfaces is poorly understood, despite its fundamental importance for molecular or biomolecular motion and molecular recognition events at biological interfaces. Here, we use fluorescence microscopy to monitor the spreading of mono-, di- and trivalent ligand molecules on a receptor-functionalized surface, and perform multiscale computer simulations to understand the surface diffusion mechanisms. Analogous to chemotaxis, we found that the spreading is directional (along a developing gradient of vacant receptor sites) and is strongly dependent on ligand valency and concentration of a competing monovalent receptor in solution. We identify multiple surface diffusion mechanisms, which we call walking, hopping and flying. The study shows that the interfacial behaviour of multivalent systems is much more complex than that of monovalent ones.

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Figure 1: Guest and host compounds, divalent thermodynamic equilibria and kinetic pathways.
Figure 2: Evaluation of spreading rates.
Figure 3: Themodynamic equilibrium concentrations and representation of rebinding probability.
Figure 4: Monte Carlo simulations.

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References

  1. Thibault-Starzyk, F., Seguin, E., Thomas, S. Daturi, M., Arnolds, H. & King, D. A. Real-time infrared detection of cyanide flip on silver-alumina NOx removal catalyst. Science 324, 1048–1051 (2009).

    Article  CAS  Google Scholar 

  2. Backus, E. H. G., Eichler, A., Kleyn, A. W. & Bonn, M. Real-time observation of molecular motion on a surface. Science 310, 1790–1793 (2005).

    Article  CAS  Google Scholar 

  3. Helenius, J., Brouhard, G., Kalaidzidis, Y., Diez, S. & Howard, J. The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends. Nature 441, 115–119 (2006).

    Article  CAS  Google Scholar 

  4. Hess, H., Clemmens, J., Qin, D., Howard, J. & Vogel, V. Light-controlled molecular shuttles made from motor proteins carrying cargo on engineered surfaces. Nano Lett. 1, 235–239 (2001).

    Article  CAS  Google Scholar 

  5. Goel, A. & Vogel, V. Harnessing biological motors to engineer systems for nanoscale transport and assembly. Nature Nanotech. 3, 465–475 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Lund, K. et al. Molecular robots guided by prescriptive landscapes. Nature 465, 206–210 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Berna, J. et al. Macroscopic transport by synthetic molecular machines. Nat. Mater. 4, 704–710 (2005).

    Article  CAS  Google Scholar 

  10. Kelly, T. R. Molecular motors: synthetic DNA-based walkers inspired by kinesin. Angew. Chem. Int. Ed. 44, 4124–4127 (2005).

    Article  CAS  Google Scholar 

  11. Badjic, J. D., Balzani, V., Credi, A., Silvi, S. & Stoddart, J. F. A molecular elevator. Science 303, 1845–1849 (2004).

    Article  CAS  Google Scholar 

  12. Feringa, B. L. In control of motion: from molecular switches to molecular motors. Acc. Chem. Res. 34, 504–513 (2001).

    Article  CAS  Google Scholar 

  13. Sakai, N. & Matile, S. G-quartet self-assembly under osmotic pressure: remote control by vesicle shrinking rather than stress. Chirality 15, 766–771 (2003).

    Article  CAS  Google Scholar 

  14. Servant, G. et al. Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science 287, 1037–1040 (2000).

    Article  CAS  Google Scholar 

  15. Ueda, M., Sako, Y., Tanaka, T., Devreotes, P. & Yanagida, T. Single-molecule analysis of chemotactic signaling in dictyostelium cells. Science 294, 864–867 (2001).

    Article  CAS  Google Scholar 

  16. Kim, M. S., Khang, G. & Lee, H. B. Gradient polymer surfaces for biomedical applications. Prog. Polym. Sci. 33, 138–164 (2008).

    Article  CAS  Google Scholar 

  17. Chang, T., Rozkiewicz, D. I., Ravoo, B. J., Meijer, E. W. & Reinhoudt, D. N. Directional movement of dendritic macromolecules on gradient surfaces. Nano Lett. 7, 978–980 (2007).

    Article  CAS  Google Scholar 

  18. Burgos, P., Zhang, Z., Golestanian, R., Leggett, G. J. & Geoghegan, M. Directed single molecule diffusion triggered by surface energy gradients. ACS Nano 3, 3235–3243 (2009).

    Article  CAS  Google Scholar 

  19. Tauk, L., Schroder, A. P., Decher, G. & Giuseppone, N. Hierarchical functional gradients of pH-responsive self-assembled monolayers using dynamic covalent chemistry on surfaces. Nature Chem. 1, 649–656 (2009).

    Article  CAS  Google Scholar 

  20. Kiessling, L. L., Gestwicki, J. E. & Strong, L. E. Synthetic multivalent ligands as probes of signal transduction. Angew. Chem. Int. Ed. 45, 2348–2368 (2006).

    Article  CAS  Google Scholar 

  21. Mammen, M., Choi, S. K. & Whitesides, G. M. Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew. Chem. Int. Ed. 37, 2754–2794 (1998).

    Article  Google Scholar 

  22. Huskens, J. et al. A model for describing the thermodynamics of multivalent host–guest interactions at interfaces. J. Am. Chem. Soc. 126, 6784–6797 (2004).

    Article  CAS  Google Scholar 

  23. Houseman, B. T. & Mrksich, M. Model systems for studying polyvalent carbohydrate binding interactions, in Host–Guest Chemistry: mimetic approaches to study carbohydrate recognition (Topics in Current Chemistry) Vol. 218 (ed. Penades, S.) 1–44 (Springer, 2002).

    Google Scholar 

  24. Ludden, M. J. W., Reinhoudt, D. N. & Huskens, J. Molecular printboards: versatile platforms for the creation and positioning of supramolecular assemblies and materials. Chem. Soc. Rev. 35, 1122–1134 (2006).

    Article  CAS  Google Scholar 

  25. Rao, J. H., Lahiri, J., Isaacs, L., Weis, R. M. & Whitesides, G. M. A trivalent system from vancomycin–D-Ala–D-Ala with higher affinity than avidin–biotin. Science 280, 708–711 (1998).

    Article  CAS  Google Scholar 

  26. Badjić, J. D., Cantrill, S. J. & Stoddart, J. F. Can multivalency be expressed kinetically? The answer is yes. J. Am. Chem. Soc. 126, 2288–2289 (2004).

    Article  Google Scholar 

  27. Onclin, S., Mulder, A., Huskens, J., Ravoo, B. J. & Reinhoudt, D. N. Molecular printboards: monolayers of β-cyclodextrins on silicon oxide surfaces. Langmuir 20, 5460–5466 (2004).

    Article  CAS  Google Scholar 

  28. Antczak, G. & Ehrlich, G. Jump processes in surface diffusion. Surf. Sci. Rep. 62, 39–61 (2007).

    Article  CAS  Google Scholar 

  29. Hla, S.-W. Scanning tunneling microscopy single atom/molecule manipulation and its application to nanoscience and technology. J. Vac. Sci. Technol. B 23, 1351–1360 (2005).

    Article  CAS  Google Scholar 

  30. Thompson, D. & Larsson, J. A. Modeling competitive guest binding to β-cyclodextrin molecular printboards. J. Phys. Chem. B 110, 16640–16645 (2006).

    Article  CAS  Google Scholar 

  31. Thompson, D. Free energy balance predicates dendrimer binding multivalency at molecular printboards. Langmuir 23, 8441–8451 (2007).

    Article  CAS  Google Scholar 

  32. Cieplak, M. & Thompson, D. Coarse-grained molecular dynamics simulations of nanopatterning with multivalent inks. J. Chem. Phys. 128, 234906 (2008).

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by the European FP6 Integrated project NaPa (A.P., H.D., J.H.; contract no. NMP4-CT-2003-500120) and by the Nanotechnology network in the Netherlands NanoNed (AGC; project no. TPC.6939). D.T. also acknowledges support from the European FP7 project FunMol (grant agreement no. 213382), Science Foundation Ireland (SFI) for computing resources at Tyndall National Institute and SFI/ Higher Education Authority for computing time at the Irish Centre for High-End Computing (ICHEC). The authors thank J. Opheusden for discussion of the Monte Carlo simulations.

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A.P., A.G.C., P.J., D.N.R. and J.H. conceived and designed the experiments. A.P. and H.H.D. performed the experimental work. A.G.C. and D.T. performed the modelling. J.H. was responsible for the overall design, direction and supervision of the project. A.P., D.T., P.J., D.N.R. and J.H. co-wrote the paper.

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Correspondence to Jurriaan Huskens.

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The authors declare no competing financial interests.

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Perl, A., Gomez-Casado, A., Thompson, D. et al. Gradient-driven motion of multivalent ligand molecules along a surface functionalized with multiple receptors. Nature Chem 3, 317–322 (2011). https://doi.org/10.1038/nchem.1005

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