Salt-Induced Dissolution of Protein Aggregates

Protein aggregation is mediated by a complex interplay of noncovalent interactions and is associated with a broad range of aspects from debilitating human diseases to the food industry and therapeutic biotechnology. Deciphering the intricate roles of noncovalent interactions is of paramount importance for the design of effective inhibitory and disaggregation strategies, which remains a formidable challenge. By using a combination of spectroscopic and microscopic tools, here we show that the surfactant-mediated protein aggregation can be modulated by an intriguing interplay of hydrophobic and electrostatic effects. Additionally, our results illuminate the unique role of salt as a potent disaggregation inducer that alters the protein-surfactant electrostatic interactions and triggers the dissolution of preformed protein aggregates resulting in restoring the native protein structure. This unusual salt-induced dissolution and refolding offers a unique approach to regulating the balance between protein self-assembly and disassembly and will offer a potent strategy to design electrostatically targeted inhibitors.

Automated summary

Protein aggregation mediated by noncovalent interactions is important for various fields and understanding the roles of these interactions is crucial for designing effective strategies. A combination of spectroscopic and microscopic tools was used to reveal that surfactant-mediated protein aggregation can be modulated by hydrophobic and electrostatic effects. Furthermore, the unique role of salt as a disaggregation inducer alters electrostatic interactions and dissolves preformed protein aggregates, offering a potential strategy for designing electrostatically targeted inhibitors.