Biphasic modulation of hen egg white lysozyme amyloid aggregation by dioctyl sulfosuccinate sodium: Effects of...

Amyloid fibrillation caused by ligand binding is a double-edged process that plays a critical role in shedding light on neurodegenerative disorders. In this work, we explored how the anionic surfactant dioctyl sulfosuccinate sodium salt (DOSS) induces amyloid fibril formation of hen egg-white lysozyme (HEWL) in a concentration-dependent manner at pH 7.5. Our biophysical studies showed that upon addition of 800 μM DOSS, HEWL undergoes structural rearrangements from α-helical to β-sheet conformations, with the highest aggregation occurring at moderate (300-1000 μM) DOSS levels. In contrast, at very high surfactant concentrations (>1000 μM), it leads to another structural modification. Molecular dynamics simulations suggested that DOSS causes subtle expansion and increased flexibility in HEWL, promoting aggregation without causing major unfolding. We further examined the roles of different cosolutes on DOSS-induced aggregates: Polyethylene Glycol 4000 (PEG 4000) helps stabilize them; sucrose suppresses aggregation by favoring the native state; and ethanol has a dual effect: it enhances aggregation at low concentrations (up to 20%) and solubilizes aggregates at higher concentrations. These results illuminate the intricate balance between surfactants and the solvent environment in directing amyloid formation. Looking ahead, these mechanistic insights could guide the development of therapies that selectively prevent harmful aggregation. Additionally, understanding these interactions is essential for designing biopharmaceutical formulations to avoid unintended protein aggregation in therapeutic products.