Molecular Origin of the Elastic State of Aqueous Hyaluronic Acid

The macroscopic mechanical properties of biological hydrogels are broadly studied and successfully mimicked in synthetic materials, but little is known about the molecular interactions that mediate these properties. Here we use two-dimensional infrared spectroscopy (2D-IR) to study the pH-induced gelation of hyaluronic acid, a ubiquitous biopolymer, which undergoes a transition from a viscous to an elastic state in a narrow pH range around 2.5. We find that the gelation originates from the enhanced formation of strong inter-chain connections, consisting of a double amide-COOH hydrogen-bond and an N-D-COO- hydrogen-bond on the adjacent sugars of the hyaluronan disaccharide unit. We confirm the enhanced inter-chain connectivity in the elastic state by AFM imaging.