title: Force spectroscopy of the interaction between mycobacterial adhesins and heparan sulphate proteoglycan receptors.
abstract: Understanding the molecular interactions between bacterial adhesion proteins (adhesins) and their receptors is essential for elucidating the molecular mechanisms of bacterial pathogenesis. Here, atomic force microscopy (AFM) is used to explore the specific interactions between the heparin-binding hemagglutinin (HBHA) from Mycobacterium tuberculosis, and heparan sulphate proteoglycan (HSPG) receptors on live A549 pneumocytes. First, we show that the specific binding forces between single HBHA-HSPG pairs, 57+/-16 pN, are similar to the forces measured earlier between HBHA and heparin molecules. Second, we mapped the distribution of single HSPG receptors on the surface of A549 cells, revealing that the proteins are widely and homogeneously exposed. Third, we observed force curves with constant force plateaus at large pulling velocities, reflecting the extraction of membrane tethers or nanotubes. These single-molecule measurements provide new avenues in pathogenesis research, particularly for elucidating the molecular basis of pathogen-host interactions.
authors.affiliation: Unité de Chimie des Interfaces, Université Catholique de Louvain, Croix du Sud 2/18, B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Dupres
authors.forename: Claire
authors.initials: C
authors.lastname: Verbelen
authors.forename: Dominique
authors.initials: D
authors.lastname: Raze
authors.forename: Frank
authors.initials: F
authors.lastname: Lafont
authors.forename: Yves F
authors.initials: YF
authors.lastname: Dufrêne
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D018625:Microscopy, Atomic Force; D009161:Mycobacterium / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D019812:Heparan Sulfate Proteoglycans; D037102:Lectins; D011994:Recombinant Proteins; C104578:heparin-binding hemagglutinin