Thiocyanate Ion (SCN-) Offers a Major Impact in Rapid Protein Amyloidosis: A Salient Role Played by Protein Solvation.

Thiocyanate (SCN^-) is known to be a naive ion abundant in biological fluids, blood, and urine. It is also used as a biomarker, as it can penetrate to the brain by crossing the blood brain barrier (BBB) and also gets into the cerebrospinal fluid (CSF) through the blood-CSF barrier. Considering its importance in human physiology, we examine the effect of SCN^- ions on three model proteins: ovalbumin (Ova), bovine serum albumin (BSA), and lysozyme (Lys). We observe that an elevated level of SCN^- (∼0.5 M) leads to an otherwise unusual instant fibrilization of all these proteins at pH 2 at ambient temperature. Field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) reveal two distinct initial amyloid-aggregated states: nucleus, protofibril, and two mature fibril states (upon 24 h of incubation): cross-linked network or matrix and bundle-like structures. Despite the structural variation of the three proteins, the formation of these morphologies depends on the counterion: Na⁺ and guanidinium (Gdm⁺). Since these processes are assisted by the associated alteration in protein hydration, we determine individual protein and salt hydration at the thus-obtained different phases using THz-FTIR spectroscopy in the 1.5-22.5 THz (50-750 cm^-1) frequency window. We found that, depending on the counterion, interfacial hydration could act either as a "lubricant" or as a "de-wetting" agent, and the findings can be a potential foundation for future handling of amyloidosis.