hyaluronanbinding

Hyaluronan-binding refers to the specific interaction between hyaluronan, a high-molecular-weight glycosaminoglycan, and a variety of proteins and cell-surface receptors. Proteins capable of binding hyaluronan are collectively called hyaladherins, and they regulate the assembly, organization, and signaling properties of the pericellular and extracellular matrix.

Molecular basis: Binding is mediated by hyaladherins that contain specialized HA-binding domains, most notably link modules, as well as other positively charged or structured surfaces that recognize the repeating disaccharide units of hyaluronan. Binding affinity and avidity depend on hyaluronan chain length, protein conformation, and multivalency. Some hyaladherins bind hyaluronan via a single site; others form multivalent interactions that promote matrix anchoring or receptor clustering.

Representative hyaladherins and receptors: CD44 is the principal cell-surface receptor for hyaluronan, implicated in adhesion, migration, and signaling. RHAMM mediates hyaluronan-dependent motility. LYVE-1 is expressed on lymphatic endothelium and binds hyaluronan for transport. TSG-6 modulates hyaluronan organization in inflammation and ECM remodeling. Other HA-binding proteins include hyaluronidases (which degrade hyaluronan) and HA receptors such as HARE/Stabilin-2, involved in endocytosis and clearance.

Biological roles: Hyaluronan binding contributes to pericellular hydration, ECM viscoelastic properties, and the regulation of cell behaviors such as proliferation, migration, and differentiation. The size of hyaluronan fragments can influence downstream signaling, with low-molecular-weight fragments often promoting inflammatory responses.

Applications: Understanding hyaluronan binding informs studies of development, wound healing, cancer, and inflammatory diseases, and hyaluronan-binding domains are used in biomaterials design, including hyaluronic acid hydrogels and targeted delivery systems.