Hyaluronan (HA) is an extracellular and cell-surface bound polysaccharide with a molecular weight that can range from a few 5000 to 20 million Daltons. It is associated with a range of disparate biological tissues and activities, and found in many vertebrate organisms. A negatively-charged glycosaminoglycan (GAG), HA is composed of the repeating disaccharide of D-glucuronic acid (GLcA) and N-acetyl-D-glucosamine (GlcNAc). Its composition and charge make HA very hydrophilic, and explain the polymer’s space filling character and the swelling of hydrated HA networks. These properties have earned HA a reputation as a biological ‘goo’ that fills connective tissues and lubricates joints. Only recently has it been recognized that HA also functions as a micro-environmental cue that co-regulates cell behavior during cell migration, morphogenesis, wound healing processes, inflammation, and tumor development.
Many of these events involve specialized HA-matrices with particular material properties. Hyaluronan in itself, however, is relatively simple chemically and stands out as the only GAG that is not sulfated. It is believed that HA’s remarkable functional and structural diversity is facilitated by HA-binding proteins that dictate the microstructure of this large macromolecule and its aggregates. NMR studies, computer simulations and physiological studies supporting this hypothesis, show that a cohort of different proteins can ‘tie-up’ the HA polymer in a multitude of unique structures.
Only few studies have investigated how protein binding with polymeric HA leads to the transformation of HA structure and to HA-rich tissues (a well-studied exception being aggrecan, a primary component of cartilage). The Curtis Lab aims to characterize HA-protein aggregates in two important contexts - in well defined solutions and in the coat of living cells.