Polysorbate 80 Controls Morphology, Structure and Stability of Human Insulin Amyloid-Like Spherulites
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Polysorbate 80 Controls Morphology, Structure and Stability of Human Insulin Amyloid-Like Spherulites. / Zhou, Xin; Galparsoro, Dirk Fennema; Madsen, Anders Østergaard; Vetri, Valeria; Weert, Marco van de; Nielsen, Hanne Mørck; Foderà, Vito.
bioRxiv, 2021.Research output: Working paper › Preprint › Research
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TY - UNPB
T1 - Polysorbate 80 Controls Morphology, Structure and Stability of Human Insulin Amyloid-Like Spherulites
AU - Zhou, Xin
AU - Galparsoro, Dirk Fennema
AU - Madsen, Anders Østergaard
AU - Vetri, Valeria
AU - Weert, Marco van de
AU - Nielsen, Hanne Mørck
AU - Foderà, Vito
PY - 2021/8/10
Y1 - 2021/8/10
N2 - Amyloid 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.
AB - Amyloid 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.
U2 - 10.1101/2021.08.10.455855
DO - 10.1101/2021.08.10.455855
M3 - Preprint
BT - Polysorbate 80 Controls Morphology, Structure and Stability of Human Insulin Amyloid-Like Spherulites
PB - bioRxiv
ER -
ID: 305111833