Preferential solvation drives polysaccharide conformation and viscoelasticity

Polysaccharide conformations are central to biological function but exhibit a strikingly counterintuitive, non-monotonic behaviour. Addition of a poorer cosolvent, such as glycerol, to aqueous polysaccharide solutions induces flexible coil → swollen → collapsed conformational transitions as the solvent quality becomes progressively poorer. Using complementary simulations, theory, and experiments, we show that preferential solvation governs the conformational transitions, where the distribution of solvent molecules around the polysaccharide chain deviates significantly from that in the bulk solution. Contrary to expectations, initial chain swelling arises from preferential binding of glycerol at lower glycerol volume fraction, whereas preferential hydration leads to a more compact (collapsed) configuration at higher glycerol volume fraction. Chains appear to conserve their total water contact via such conformational reconfigurations, which map directly onto viscoelastic response; a phenomenon that may be greatly accentuated in polysaccharides. Results are explained from the perspective of Kirkwood-Buff solution theory and solvent entropic penalties, which extend beyond the Flory-type mean-field description. A tentatively unified behaviour can be observed across complex polysaccharides, including pectin, as well as other linear and branched polysaccharides such as agar, alginate, carboxymethylcellulose, and dextran, suggesting potential fundamental significance for biological and industrial aspects of glycoscience.