Large-scale polymorphism and auto-catalytic effect in insulin fibrillogenesis

TY - JOUR

T1 - Large-scale polymorphism and auto-catalytic effect in insulin fibrillogenesis

AU - Foderà, Vito

AU - van de Weert, Marco

AU - Vestergaard, Bente

PY - 2010/9/21

Y1 - 2010/9/21

N2 - Under specific conditions the protein hormone insulin is prone to form amyloid fibrils and is widely used as a model system to study fibril formation mechanisms. In this work we studied thermally induced fibril formation of insulin in acidic solutions. We mainly focused on the effect of the initial protein concentration on the final fibril morphology and the connection between morphology and secondary nucleation mechanisms. Atomic force microscopy (AFM) analysis revealed a significant fibril polymorphism on the macroscopic level dependent on protein concentration, ranging from thin and elongated fibrils to highly complex superstructures. Moreover, amyloid superstructures formed at high insulin concentration resulted in a lower propensity in being stained by Thioflavin T (ThT) and, for these structures, a reduced catalytic effect in seeding experiments was also detected. These results suggest a crucial involvement of the macroscopic properties of fibril surfaces in determining secondary nucleation pathways in insulin fibrillation.

AB - Under specific conditions the protein hormone insulin is prone to form amyloid fibrils and is widely used as a model system to study fibril formation mechanisms. In this work we studied thermally induced fibril formation of insulin in acidic solutions. We mainly focused on the effect of the initial protein concentration on the final fibril morphology and the connection between morphology and secondary nucleation mechanisms. Atomic force microscopy (AFM) analysis revealed a significant fibril polymorphism on the macroscopic level dependent on protein concentration, ranging from thin and elongated fibrils to highly complex superstructures. Moreover, amyloid superstructures formed at high insulin concentration resulted in a lower propensity in being stained by Thioflavin T (ThT) and, for these structures, a reduced catalytic effect in seeding experiments was also detected. These results suggest a crucial involvement of the macroscopic properties of fibril surfaces in determining secondary nucleation pathways in insulin fibrillation.

U2 - 10.1039/c0sm00169d

DO - 10.1039/c0sm00169d

M3 - Journal article

SN - 1744-683X

VL - 6

SP - 4413

EP - 4419

JO - Soft Matter

JF - Soft Matter

IS - 18

ER -