Preferential Binding\nof Cations Modulates Electrostatically\nDriven Protein Aggregation and Disaggregation

Protein aggregation resulting in either ordered amyloids\nor amorphous\naggregates is not only restricted to deadly human diseases but also\nassociated with biotechnological challenges encountered in the therapeutic\nand food industries. Elucidating the key structural determinants of\nprotein aggregation is important to devise targeted inhibitory strategies, but it still remains\na formidable task owing to the underlying hierarchy, stochasticity,\nand complexity associated with the self-assembly processes. Additionally,\nalterations in solution pH, salt types, and ionic strength modulate\nvarious noncovalent interactions, thus affecting the protein aggregation\npropensity and the aggregation kinetics. However, the molecular origin\nand a detailed understanding of the effects of weakly and strongly\nhydrated salts on protein aggregation and their plausible roles in\nthe dissolution of aggregates remain elusive. In this study, using\nfluorescence and circular dichroism spectroscopy in combination with\nelectron microscopy and light scattering techniques, we show that\nthe ionic size, valency, and extent of hydration of cations play a\ncrucial role in regulating the protein aggregation and disaggregation\nprocesses, which may elicit unique methods for governing the balance\nbetween protein self-assembly and disassembly.