UC Santa Barbara

The biopolymer hyaluronic acid (HA) is ubiquitous in extracellular spaces and forms complexes with proteins and proteoglycans that contribute to tissue mechanical properties, provide lubrication at biointerfaces, and affect cell adhesion and motility. It is not well-understood how structural features within single HA chains control its biological roles and its potential for use in biomaterials. HA's structural length scales (persistence length, charge spacing) are intermediate relative to other biopolymers; this makes it a useful model system for studying polyelectrolyte physics. We use magnetic tweezers to investigate how salt and HA-binding ligands can modify its random coil structure.

We present data on HA's behavior in mixed valence salt solutions, and find a regime of conformational insensitivity to ionic strength. Experiments on another flexible charged biopolymer, single-stranded DNA, confirm the effect is a general electrostatic phenomenon. With simulations and theory, we build a picture of how ion exchange within a counterion-rich layer near the chain counteracts changes in the bulk ionic strength. We also use magnetic tweezers to measure changes in HA structure associated with the formation of HA-proteoglycan bottlebrush complexes. As the large proteoglycan aggrecan binds, it induces tension in the central HA chain. Using established bottlebrush theory, we connect this tension to structural features of aggrecan. Overall, we find magnetic tweezers are sensitive to HA's random coil structure and its modification by solute interactions.