Anionic surfactant causes dual conformational changes in insulin.

Area of Science:

• Biochemistry
• Protein aggregation studies
• Neurodegenerative disease research

Background:

• Amyloid fibrillation is a key process in neurodegenerative diseases.
• Sodium dodecyl sulfate (SDS) is known to accelerate amyloid fibrillation in vitro.
• The precise molecular mechanisms of SDS-induced amyloid formation remain unclear.

Purpose of the Study:

• To investigate the effect of sodium dodecyl sulfate (SDS) on insulin amyloid fibrillation.
• To explore the influence of pH (7.4 and 2.0) on SDS-mediated insulin aggregation.
• To elucidate the molecular mechanisms underlying surfactant-induced protein fibrillation.

Main Methods:

• Incubation of insulin with varying concentrations of SDS at pH 7.4 and 2.0.
• Analysis of protein aggregation using techniques to detect secondary structure (e.g., cross-β sheet, alpha-helix).
• Assessment of the impact of salt presence and SDS concentration on preformed aggregates.

Main Results:

• Insulin formed amyloid-like aggregates with SDS at pH 2.0 within a specific concentration range (0.05–1.8 mM).
• Insulin remained soluble at pH 2.0 with SDS concentrations >1.8 mM and at all tested SDS concentrations at pH 7.4.
• Aggregated insulin exhibited cross-β sheet structure, transitioning to more alpha-helix with increased SDS; aggregation was salt-independent but reversible at high SDS concentrations.

Conclusions:

• SDS can induce insulin amyloid fibrillation at acidic pH (2.0) via electrostatic and hydrophobic interactions.
• The pH-dependent behavior and reversibility of SDS-induced insulin aggregation provide insights into surfactant-protein interactions.
• This study contributes to understanding the mechanisms of surfactant-mediated amyloid formation in proteins like insulin.