Glycosaminoglycans as Polyelectrolytes: Charge, Interactions, and Applications.

Glycosaminoglycans (GAGs) are linear, negatively charged biopolymers that modulate complex biological processes, such as blood coagulation, immune regulation, or viral entry. Their sulfation pattern and chain length govern how strongly they bind to other physiologically relevant species. Most of these interactions rely on electrostatic forces facilitated by the strong polyanionic properties of GAGs; therefore, considering these from a polyelectrolyte vantage point can help understand how such charge-based, often transient interactions contribute to physiological and pathological processes. While the different GAG classes share key electrostatic properties, they exhibit unique structural features that shape their function. Here, it is highlighted on how modern separation and analytical tools exploit the polyanionic character of GAGs to dissect subtle structural details. For these, the fundamental description of their charge-charge interactions is crucial. With this knowledge, modified GAGs, synthetic GAG mimetics, or GAG-binding molecules can be designed that replicate or refine their key properties and show promise for therapeutic and biomedical applications. Altogether, recognizing the importance of GAGs as polyelectrolytes provides vital knowledge on how their charge distribution mediates crucial biomolecular interactions in health and disease, and thus it helps complete our knowledge on fundamentally important biopolymers.