Article | Published:

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

Nature Chemistry volume 3, pages 317322 (2011) | Download Citation

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.

  • Compound C45H60N2O11S2

    2-(2-{2-[2-(Adamantan-1-yloxy)ethoxy]ethoxy}ethoxy)ethoxy-lissamine ester

  • Compound C70H97N3O16S2

    3,5-Bis[2-(2-{2-[2-(adamantan-1-yloxy)ethoxy]ethoxy}ethoxy)ethoxy]benzyl-lissamide

  • Compound C87H125N3O21S2

    3,4,5-Tris[2-(2-{2-[2-(adamantan-1-yloxy)ethoxy]ethoxy}ethoxy)ethoxy]phenyl-lissamide

  • Compound C43H69NO10

    3,5-Bis[2-(2-{2-[2-(adamantan-1-yloxy)ethoxy]ethoxy}ethoxy)ethoxy]benzylamine

  • Compound C42H70O35

    β-Cyclodextrin

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , , , & Real-time infrared detection of cyanide flip on silver-alumina NOx removal catalyst. Science 324, 1048–1051 (2009).

  2. 2.

    , , & Real-time observation of molecular motion on a surface. Science 310, 1790–1793 (2005).

  3. 3.

    , , , & The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends. Nature 441, 115–119 (2006).

  4. 4.

    , , , & Light-controlled molecular shuttles made from motor proteins carrying cargo on engineered surfaces. Nano Lett. 1, 235–239 (2001).

  5. 5.

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

  6. 6.

    , , & A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205 (2010).

  7. 7.

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

  8. 8.

    , & A synthetic small molecule that can walk down a track. Nature Chem. 2, 96–101 (2010).

  9. 9.

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

  10. 10.

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

  11. 11.

    , , , & A molecular elevator. Science 303, 1845–1849 (2004).

  12. 12.

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

  13. 13.

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

  14. 14.

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

  15. 15.

    , , , & Single-molecule analysis of chemotactic signaling in dictyostelium cells. Science 294, 864–867 (2001).

  16. 16.

    , & Gradient polymer surfaces for biomedical applications. Prog. Polym. Sci. 33, 138–164 (2008).

  17. 17.

    , , , & Directional movement of dendritic macromolecules on gradient surfaces. Nano Lett. 7, 978–980 (2007).

  18. 18.

    , , , & Directed single molecule diffusion triggered by surface energy gradients. ACS Nano 3, 3235–3243 (2009).

  19. 19.

    , , & Hierarchical functional gradients of pH-responsive self-assembled monolayers using dynamic covalent chemistry on surfaces. Nature Chem. 1, 649–656 (2009).

  20. 20.

    , & Synthetic multivalent ligands as probes of signal transduction. Angew. Chem. Int. Ed. 45, 2348–2368 (2006).

  21. 21.

    , & Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew. Chem. Int. Ed. 37, 2754–2794 (1998).

  22. 22.

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

  23. 23.

    & 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).

  24. 24.

    , & Molecular printboards: versatile platforms for the creation and positioning of supramolecular assemblies and materials. Chem. Soc. Rev. 35, 1122–1134 (2006).

  25. 25.

    , , , & A trivalent system from vancomycin–D-Ala–D-Ala with higher affinity than avidin–biotin. Science 280, 708–711 (1998).

  26. 26.

    , & Can multivalency be expressed kinetically? The answer is yes. J. Am. Chem. Soc. 126, 2288–2289 (2004).

  27. 27.

    , , , & Molecular printboards: monolayers of β-cyclodextrins on silicon oxide surfaces. Langmuir 20, 5460–5466 (2004).

  28. 28.

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

  29. 29.

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

  30. 30.

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

  31. 31.

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

  32. 32.

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

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.

Author information

Affiliations

  1. Molecular Nanofabrication Group, MESA+ Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands

    • András Perl
    • , Alberto Gomez-Casado
    • , Henk H. Dam
    • , Pascal Jonkheijm
    • , David N. Reinhoudt
    •  & Jurriaan Huskens
  2. Tyndall National Institute, University College Cork, College Road, Cork, Ireland

    • Damien Thompson

Authors

  1. Search for András Perl in:

  2. Search for Alberto Gomez-Casado in:

  3. Search for Damien Thompson in:

  4. Search for Henk H. Dam in:

  5. Search for Pascal Jonkheijm in:

  6. Search for David N. Reinhoudt in:

  7. Search for Jurriaan Huskens in:

Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jurriaan Huskens.

Supplementary information

PDF files

  1. 1.

    Supplementary information

    Supplementary information

Videos

  1. 1.

    Supplementary information

    Supplementary Movie S1

  2. 2.

    Supplementary information

    Supplementary Movie S2

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nchem.1005

Further reading