Mechanistic insights into the modulatory effects of Hofmeister ions and small molecule additives on the aggregation of food proteins

Abstract

Aberrant protein folding leads to the formation of protein amyloids and amorphous aggregates. Various experimental conditions have been employed to obtain the protein aggregates such as pH, temperature, ionic strength, additives, post-translational modifications, etc. in order to understand the plausible mechanisms underlying aggregation. Although amyloids have gained considerable attention, owing to their pathological significance, amorphous aggregates are not much explored. Based on the literature survey, we concluded that salts and salt concentration affect kinetics of protein aggregation as well as the morphology of the aggregates. However, effect of salt type and salt concentration during the formation of protein amorphous aggregates in the presence of charged additive remains elusive. Here, we have discussed the modulatory role of Hofmeister ions (both cations as well as anions) during protein aggregation. By using a combination of spectroscopic and microscopic tools, we showed that the surfactant-mediated protein aggregation can be modulated by an intriguing interplay of hydrophobic and electrostatic effects. We also showed that the ionic size, valency, and extent of hydration of Hofmeister ions play a crucial role in regulating the protein aggregation and disaggregation processes, which may elicit unique methods for governing the balance between protein self-assembly and disassembly. Overall, this unusual salt-induced dissolution and refolding offers a unique approach to regulate the balance between protein self-assembly and disassembly and will offer a potent strategy to design electrostatically-targeted inhibitors. Further, we also investigated into the aggregation of one protein in presence of another protein via liquid-liquid phase separation in order to understand the mechanisms underlying the liquid-to-solid transition of globular egg white proteins.