Sucrose modulates insulin amyloid-like fibril formation: effect on the aggregation mechanism and fibril morphology

TY - JOUR

T1 - Sucrose modulates insulin amyloid-like fibril formation: effect on the aggregation mechanism and fibril morphology

AU - Marasini, Carlotta

AU - Foderà, Vito

AU - Vestergaard, Bente

PY - 2017

Y1 - 2017

N2 - Co-solutes, such as sugars, are used in in vitro protein aggregation experiments to mimic crowding and, in general, complex environments. Sugars often increase the stability of the native protein structure by affecting inter- and intramolecular protein–protein interactions. This, in turn, modifies the protein self-assembly pathways. Using a combination of fluorescence spectroscopy, synchrotron radiation circular dichroism and transmission electron microscopy, we study the kinetics of formation and structural properties of human insulin fibrils in the presence of sucrose. The presence of sucrose results in a delay of the onset of fibrillation. Moreover, it leads to a dramatic change in both the morphology and overall amount of fibrils. Our results emphasize that the detailed composition of protein surroundings likely influences not only the fibrillation kinetics but also the balance between different species, potentially determining fibril strains with different biological activities. This aspect is crucial in the etiology of pathologies associated with amyloidosis.

AB - Co-solutes, such as sugars, are used in in vitro protein aggregation experiments to mimic crowding and, in general, complex environments. Sugars often increase the stability of the native protein structure by affecting inter- and intramolecular protein–protein interactions. This, in turn, modifies the protein self-assembly pathways. Using a combination of fluorescence spectroscopy, synchrotron radiation circular dichroism and transmission electron microscopy, we study the kinetics of formation and structural properties of human insulin fibrils in the presence of sucrose. The presence of sucrose results in a delay of the onset of fibrillation. Moreover, it leads to a dramatic change in both the morphology and overall amount of fibrils. Our results emphasize that the detailed composition of protein surroundings likely influences not only the fibrillation kinetics but also the balance between different species, potentially determining fibril strains with different biological activities. This aspect is crucial in the etiology of pathologies associated with amyloidosis.

U2 - 10.1039/C6RA25872G

DO - 10.1039/C6RA25872G

M3 - Journal article

SN - 2046-2069

VL - 7

SP - 10487

EP - 10493

JO - RSC Advances

JF - RSC Advances

ER -