Polysorbate 80 controls Morphology, structure and stability of human insulin Amyloid-Like spherulites

6533b82cfe1ef96bd128f590

RESEARCH PRODUCT

Polysorbate 80 controls Morphology, structure and stability of human insulin Amyloid-Like spherulites

Xin Zhou Anders Ø. Madsen Vito Foderà Hanne Mørck Nielsen Valeria Vetri Dirk Fennema Galparsoro Marco Van De Weert

subject

Amyloid-like Spherulites Fluorescence Lifetime Imaging Aggregate Stability Polysorbate 80 Protein Formulations Amyloid Morphology (linguistics)Amyloid Chemistry Insulin medicine.medical_treatment Intermolecular force Polysorbates Polyvinyl alcohol Surfaces Coatings and Films Electronic Optical and Magnetic Materials Biomaterials Surface-Active Agents chemistry.chemical_compound Molecular dynamics Colloid and Surface Chemistry Pulmonary surfactant Critical micelle concentration medicine Biophysics Humans Insulin Micelles

description

AbstractAmyloid protein aggregates are not only associated with neurodegenerative diseases and may also occur as unwanted by-products in protein-based therapeutics. Surfactants are often employed to stabilize protein formulations and reduce the risk of aggregation. However, surfactants alter protein-protein interactions and may thus modulate the physicochemical characteristics of any aggregates formed. Human insulin aggregation was induced at low pH in the presence of varying concentrations of the surfactant polysorbate 80. Various spectroscopic and imaging methods were used to study the aggregation kinetics, as well as structure and morphology of the formed aggregates. Molecular dynamics simulations were employed to investigate the initial interaction between the surfactant and insulin. Addition of polysorbate 80 slowed down, but did not prevent, aggregation of insulin. Amyloid spherulites formed under all conditions, with a higher content of intermolecular beta-sheets in the presence of the surfactant above its critical micelle concentration. In addition, a denser packing was observed, leading to a more stable aggregate. Molecular dynamics simulations suggested a tendency for insulin to form dimers in the presence of the surfactant, indicating a change in protein-protein interactions. It is thus shown that surfactants not only alter aggregation kinetics, but also affect physicochemical properties of any aggregates formed.

year	journal	country	edition	language
2022-01-01

10.1016/j.jcis.2021.09.132 http://hdl.handle.net/10447/542323