Self-Organization Pathways and Spatial Heterogeneity in Insulin Amyloid Fibril Formation

Maurizio Leone, Bruno Giuseppe Pignataro, Sebastiano Cataldo, Vito Foderà, Maurizio Leone, Fabio Librizzi

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35 Citazioni (Scopus)

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 originaleEnglish
pagine (da-a)10830-10837
Numero di pagine8
RivistaJOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL
Volume113
Stato di pubblicazionePublished - 2009

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insulin
Insulin
Amyloid
proteins
Proteins
Nucleation
Agglomeration
nucleation
hormones
Hormones
staining
Light scattering
low concentrations
Atomic force microscopy
light scattering
Fluorescence
atomic force microscopy
fluorescence
Molecules
Kinetics

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cita questo

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title = "Self-Organization Pathways and Spatial Heterogeneity in Insulin Amyloid Fibril Formation",
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.",
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T1 - Self-Organization Pathways and Spatial Heterogeneity in Insulin Amyloid Fibril Formation

AU - Leone, Maurizio

AU - Pignataro, Bruno Giuseppe

AU - Cataldo, Sebastiano

AU - Foderà, Vito

AU - Leone, Maurizio

AU - Librizzi, Fabio

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10447/36316

M3 - Article

VL - 113

SP - 10830

EP - 10837

JO - JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL

JF - JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL

SN - 1520-6106

ER -