Quantitative glycomics from fluidic glycan microarrays.
A hallmark of cell-surface processes involving glycans is their multivalent interaction with glycan binding proteins (GBPs). Such a multivalent interaction depends critically on the mobility and density of signaling molecules on the membrane surface. While glycan microarrays have been used in exploring multivalent interactions, the lack of mobility and the difficulty in controlling surface density both limit their quantitative applications. Here we apply a fluidic glycan microarray, with glycan density varying for orders of magnitude, to profile cell surface interaction using a model system, the adhesion of Escherichia coli to mannose. We show the quantitative determination of monovalent and multivalent adhesion channels; the latter can be inhibited by nanopartices presenting a high density of mannosyl groups. These results reveal a new E. coli adhesion mechanism: the switching in the FimH adhesion protein avidity from monovalent to multivalent as the density of mobile mannosyl groups increases; such avidity switching enhances binding affinity and triggers multiple fimbriae anchoring. Affinity enhancement toward FimH has only been observed before for oligo-mannose due to the turn on of secondary interactions outside the mannose binding pocket. We suggest that the new mechanism revealed by the fluidic microarray is of general significance to cell surface interactions: the dynamic clustering of simple sugar groups (homogeneous or heterogeneous) on the fluidic membrane surface may simulate the functions of complex glycan molecules.
Zhu
X-Y
XY
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA. zhu@cm.utexas.edu
Holtz
Bryan
B
Wang
Yini
Y
Wang
Lai-Xi
LX
Orndorff
Paul E
PE
Guo
Athena
A
D018830:Adhesins, Escherichia coli / Q000737:chemistry / Q000378:metabolism; D001422:Bacterial Adhesion; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D004926:Escherichia coli / Q000737:chemistry / Q000502:physiology; D036781:Fimbriae Proteins / Q000737:chemistry / Q000378:metabolism; D054794:Glycomics / Q000379:methods*; D008358:Mannose / Q000737:chemistry / Q000378:metabolism; D046228:Microarray Analysis / Q000379:methods*; D046210:Microfluidic Analytical Techniques; D011134:Polysaccharides / Q000032:analysis* / Q000378:metabolism
D018830:Adhesins, Escherichia coli; D011134:Polysaccharides; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; D008358:Mannose