Sweet but strong: how the glycocalyx strengthens pathogen binding

1 September 2017

A study entitled “N-glycan mediated adhesion strengthening during pathogen-receptor binding revealed by cell-cell force spectroscopy” was recently accepted for publication in Scientific Reports. This work was done by Joost te Riet and colleagues in the group of Alessandra Cambi, theme Nanomedicine, in collaboration with Carl Figdor, theme Cancer development and immune defense.

‘In this study we demonstrated that the pericellular layer of sugar chains (named glycocalyx) can help strengthening host-pathogen interactions mediated by pathogen-recognition receptors. By using an atomic force microscope (AFM) – a very sensitive technique to manipulate single cells available at the Radboudumc Technology Center MIC – we were able to measure the binding strength between single human dendritic cells and single cells of the fungus Candida albicans. Using the AFM as cell nano-manipulator, we brought one host cell into contact with a fungal cell and subsequently measured the mechanical force necessary to part them apart. These interaction forces were significantly lower after blocking the glycocalyx, indicating that this sugar layer provides an additional mechanical force to the immune cells to bind the fungus more strongly.’

Although the primary players in these interactions are receptors on the immune cells that bind to specific molecules on the Candida cell wall, the glycocalyx of the immune cells now appears responsible for strengthening these interactions by increasing cell stiffening at the contact site with the pathogen.

These findings demonstrate for the first time the direct involvement of this cell sugar layer in strengthening cell-pathogen interactions and put forward a possible role for the glycocalyx as extracellular ”skeleton”. This exo-skeleton could possibly synergize with the intracellular actin cytoskeleton to reinforce cell-pathogen interactions, eventually facilitating pathogen uptake by the immune cell.

Unraveling the repertoire of molecular mechanisms involved in host-pathogen interactions will not only increase our understanding of these processes but will also on a long run provide novel leads for treatments of infectious diseases. Moreover, glycocalyx defects are associated with various pathologies, such as cancer, diabetes and congenital disorders of glycosylation and are known to affect the immune system, thus making these initial results relevant to a broad scientific community. 

Link to the publication on PubMed you can find here.
 Alessandra Cambi