Single-Molecule Force Spectroscopy Studies of Hyaluronic Acid Motivate a Simple Model for Flexible Polyelectrolyte Interactions with Multivalent Ions

Hyaluronic acid (HA) is a charged linear polysaccharide abundant in extracellular spaces. Its solution conformation and mechanical properties help structure the environment outside of cells and are of interest for biomaterials development. Trivalent cations are particularly relevant to HA gel materials as they interact strongly with the polymer and can form ionic crosslinks. To investigate the nature of HA-trivalent interactions, we use magnetic tweezers to apply biological-scale stretching forces to individual HA chains in the presence of trivalent cations. Based on these experiments, we develop a simple model which qualitatively predicts the behavior of the HA-trivalent system. We propose that the HA chain wraps around the cation to maximize contact between the anionic carboxylate groups and the trivalent cation. We observe a large decrease in experimentally measured persistence length consistent with the short length-scale bending in the wrapping model. We predict that additional monovalent salt can screen away the interaction in a manner dependent on the ion radius, and confirm the existence of this effect in experiments. The model is extended to describe other flexible polyelectrolytes interacting with ions.