Interfacial Solute Organization Governs Mixed-Osmolyte Compatibility under Salt Stress.

Abstract

Mixed osmolytes protect charged biomolecular and nanomaterial interfaces under salt stress, but their combined effects are often nonadditive. Here we identify interfacial solute organization as a molecular criterion that determines whether a mixture is protective or antagonistic via combining computer simulations and experiments. All-atom simulations of negatively charged α-quartz nanoslabs, supported by SHINERS and ATR-FTIRS experiments on silica surfaces, show that urea weakens glycine-mediated protection but strengthens TMAO- and betaine-mediated protection. The difference arises from nanoscale organization: urea associates with glycine at the charged interface, suppressing glycine-driven cation displacement and reducing intersurface repulsion, whereas urea remains spatially independent of TMAO and betaine, allowing their ion-modulating effects to combine constructively. The same directional behavior is reproduced in Aβ(1-40) dimerization simulations and Aβ-derived AcKE aggregation kinetic experiments. These results establish interfacial solute organization as a transferable rule for designing multicomponent protective environments.