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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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.
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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