Abstract
At high temperature and low pH, the protein hormone insulin is highly prone to form amyloid fibrils, and for this reason it is widely used as a model system to study fibril formation mechanisms. In this work, we focused on insulin aggregation mechanisms occurring in HCl solutions (pH 1.6) at 60 °C. By means of in situ Thioflavin T (ThT) staining, the kinetics profiles were characterized as a function of the protein concentration, and two concurrent aggregation pathways were pointed out, being concentration dependent. In correspondence to these pathways, different morphologies of self-assembled protein molecules were detected by atomic force microscopy images also evidencing the presence of secondary nucleation processes as a peculiar mechanism for insulinfibrillation. Moreover, combining ThT fluorescence and light scattering, the early stages of the process were analyzed in the low concentration regime, pointing out a pronounced spatial heterogeneity in the formation of the first stable fibrils in solution and the onset of the secondary nucleation pathways.
Lingua originale | English |
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pagine (da-a) | 10830-10837 |
Numero di pagine | 8 |
Rivista | JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL |
Volume | 113 |
Stato di pubblicazione | Published - 2009 |
All Science Journal Classification (ASJC) codes
- ???subjectarea.asjc.1600.1606???
- ???subjectarea.asjc.2500.2508???
- ???subjectarea.asjc.2500.2505???