Force Spectroscopy of the Interaction Between Mycobacterial Adhesins and Heparan Sulphate Proteoglycan Receptors

✍ Scribed by Vincent Dupres; Claire Verbelen; Dominique Raze; Frank Lafont; Yves F. Dufrêne

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 344 KB
• Volume: 10
• Category: Article
• ISSN: 1439-4235
• DOI: 10.1002/cphc.200900208

✦ Synopsis

Abstract

New avenues in pathogenesis research: Single‐molecule measurements using AFM elucidate the specific binding forces between pathogen–host interactions. A bacterial adhesin (HBHA) on the AFM tip detects single HSPG receptors directly on living host cells (see figure). In vivo HBHA‐HSPG binding forces are similar to those measured in vitro for HBHA‐heparin complexes.magnified image

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.__