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Direct visualization of superselective colloid-surface binding mediated by multivalent interactions

Proceedings of the National Academy of Sciences, vol. 118

Abstract

Reliably distinguishing between cells based on minute differences in receptor density is crucial for cell-cell or virus-cell recognition, the initiation of signal transduction, and selective targeting in directed drug delivery. Such sharp differentiation between different surfaces based on their receptor density can only be achieved by multivalent interactions. Several theoretical and experimental works have contributed to our understanding of this "superselectivity." However, a versatile, controlled experimental model system that allows quantitative measurements on the ligand-receptor level is still missing. Here, we present a multivalent model system based on colloidal particles equipped with surface-mobile DNA linkers that can superselectively target a surface functionalized with the complementary mobile DNA-linkers. Using a combined approach of light microscopy and Foerster resonance energy transfer (FRET), we can directly observe the binding and recruitment of the ligand-receptor pairs in the contact area. We find a nonlinear transition in colloid-surface binding probability with increasing ligand or receptor concentration. In addition, we observe an increased sensitivity with weaker ligand-receptor interactions, and we confirm that the timescale of binding reversibility of individual linkers has a strong influence on superselectivity. These unprecedented insights on the ligand-receptor level provide dynamic information into the multivalent interaction between two fluidic membranes mediated by both mobile receptors and ligands and will enable future work on the role of spatial-temporal ligand-receptor dynamics on colloid-surface binding.

Authors 5

  1. Leiden University · Delft University of Technology

    Affiliation as printed

    Department of Bionanoscience, Technical University Delft, 2629 HZ Delft, The Netherlands;

    Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden Institute of Physics, 2300 RA Leiden, The Netherlands;

    Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden Institute of Physics, 2300 RA Leiden, The Netherlands

  2. Thomas Young Centre · Imperial College London

    Affiliation as printed

    Department of Materials, Imperial College London, SW72AZ London, United Kingdom;

    Thomas Young Centre, Imperial College London, SW72AZ London, United Kingdom

    Imperial College London

  3. Thomas Young Centre · Imperial College London

    Affiliation as printed

    Department of Materials, Imperial College London, SW72AZ London, United Kingdom;

    Thomas Young Centre, Imperial College London, SW72AZ London, United Kingdom

    Imperial College London

  4. Liedewij Laan corresponding

    Delft University of Technology

    Affiliation as printed

    Department of Bionanoscience, Technical University Delft, 2629 HZ Delft, The Netherlands;

    Department of Bionanoscience, Technical University Delft, 2629 HZ Delft, The Netherlands; l.laan@tudelft.nl kraft@physics.leidenuniv.nl

  5. Leiden University

    Affiliation as printed

    Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden Institute of Physics, 2300 RA Leiden, The Netherlands;

    Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden Institute of Physics, 2300 RA Leiden, The Netherlands; l.laan@tudelft.nl kraft@physics.leidenuniv.nl

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References 45