Molecular mechanism for structure-dependent ligand recognition of the hyaluronan receptor

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Hyaluronan (HA) is an extremely simple polysaccharide composed of repeating disaccharide units in which N-acetylglucosamine and glucuronic acid are linked together by alternating β-1,3 and β-1,4 linkages. The simple repeating structure of HA is involved in both a number of important cell behaviors and maintenance of tissue architecture. The multiple properties of HA depend largely on its molecular size, tissue concentration and the interaction with binding molecules. In this study, I examined the structural features of HA by scanning probe microscope. The three dimensional structure of HA changed dependently on its chain length and concentration. To examine the importance of HA structure in the ligand recognition of HA receptor CD44, I analyzed both affinity and kinetics of HA-CD44 interactions by surface plasmon resonance (SPR), and found that HA-binding molecule versican increased the affinity of CD44 to HA, suggesting that versican enhances the HA-CD44 interaction by altering HA structure. I then examined the effect of HA-binding molecule SHAP on the CD44-HA interaction-mediated cell adhesion. Under both static and flowing conditions, CD44-expressing cells adhered preferentially to the immobilized SHAP-HA complex than to HA alone, suggesting that SHAP enhances the interaction by increasing the avidity of HA to CD44.