Atomic force microscopy imaging of supramolecular organization of hyaluronan and its receptor CD44

Hyaluronan is a major component of extracellular matrix and involved in a variety of important biological processes such as cell motility, proliferation, differentiation, and survival. However, the structure of hyaluronan and the mode of interaction between hyaluronan and its receptor remain to be fully elucidated. Here, we visualized directly the structure of hyaluronan by nanoscale imaging using atomic force microscopy (AFM), and analyzed the pattern of interaction with its cell surface receptor CD44. We observed by AFM that hyaluronan formed honeycomb-like network structures, to which the recombinant protein of CD44 extracellular domain intensively adhered. The pattern of the meshwork varied with the concentration of hyaluronan and also with its molecular weight. These observations suggest that the network structure might account for the properties of hyaluronan of being like an elastic gel at high concentration, and that the structure varying in relation to the molecular weight may cause the difference in the biological activities of the hyaluronan.