Scientific Reports (Jul 2017)

N-glycan mediated adhesion strengthening during pathogen-receptor binding revealed by cell-cell force spectroscopy

  • Joost te Riet,
  • Ben Joosten,
  • Inge Reinieren-Beeren,
  • Carl G. Figdor,
  • Alessandra Cambi

DOI
https://doi.org/10.1038/s41598-017-07220-w
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 12

Abstract

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Abstract Glycan-protein lateral interactions have gained increased attention as important modulators of receptor function, by regulating surface residence time and endocytosis of membrane glycoproteins. The pathogen-recognition receptor DC-SIGN is highly expressed at the membrane of antigen-presenting dendritic cells, where it is organized in nanoclusters and binds to different viruses, bacteria and fungi. We recently demonstrated that DC-SIGN N-glycans spatially restrict receptor diffusion within the plasma membrane, favoring its internalization through clathrin-coated pits. Here, we investigated the involvement of the N-glycans of DC-SIGN expressing cells on pathogen binding strengthening when interacting with Candida fungal cells by using atomic force microscope (AFM)-assisted single cell-pathogen adhesion measurements. The use of DC-SIGN mutants lacking the N-glycans as well as blocking glycan-mediated lateral interactions strongly impaired cell stiffening during pathogen binding. Our findings demonstrate for the first time the direct involvement of the cell membrane glycans in strengthening cell-pathogen interactions. This study, therefore, puts forward a possible role for the glycocalyx as extracellular cytoskeleton contributing, possibly in connection with the intracellular actin cytoskeleton, to optimize strengthening of cell-pathogen interactions in the presence of mechanical forces.