Novel Functions and Binding Mechanisms of Carbohydrate-Binding Proteins Determined by Force Measurements

Deborah      E. Leckband

Abstract

Cell surface carbohydrates are important targets for many cell surface receptors, and they mediate crucial biological processes ranging from pathogen infectivity to neutrophil adhesion to drug targeting. A central challenge is to identify relationships between lectin architecture and function that influence the adhesion strength, avidity, and kinetics of receptor-glycan bonds. This information is central both to understanding recognition mechanisms and to developing effective therapeutic agents for drug targeting or for preventing infection. Increasingly, force probes are used to assess structure activity relationships of both the glycan ligands and the receptors that bind them, as well as molecular mechanisms underlying binding and adhesion. This review describes recent advances in the use of different force measurement techniques to quantify receptor-glycan bond parameters, and to identify novel features of molecular mechanisms underlying recognition and adhesion. The examples discussed focus in particular on single bond rupture, surface force measurements, and micropipette manipulation. This review emphasizes the often-unique information obtained from studies of lectin interactions with carbohydrate ligands that complement more common structure determinations and solution binding studies.

Keywords: Adhesin, atomic force microscopy, binding kinetics, catch bond, force measurements, lectin, surface force apparatus, Leukocyte, Carbohydrates, inflammatory cytokines