Dissecting ion-specific from electrostatic salt effects on amyloid fibrillation: A case study of insulin.

Journal Article (Journal Article)

Diseases like Alzheimer, type II diabetes mellitus, and others go back to fibril formation of partially unfolded proteins. The impact of sodium, potassium, choline, guanidinium, and 1-ethyl-3-methylimidazolium chloride on the fibrillation kinetics of insulin in an acid-denaturing solvent environment is studied by fluorescence spectroscopy using thioflavin T as a fibril-specific stain. The fibrillation kinetics reveal a sigmoidal behavior, characterized by the lag time τlag and the maximum elongation rate k of the fibrils. Up to ionic strengths of about 70 mM, the elongation rate increases with salt concentration. This increase is nonspecific with regard to the salts. Below ionic strengths of ∼50 mM, it can be explained by a Debye-Hückel type model, indicating a dominant role of Coulomb interactions between the charged reactants and products screened by the ionic environment. At higher ionic strength, the elongation rates pass maxima, followed by a Hofmeister type ion-specific decrease. There is a correlation between the lag time τlag and the inverse elongation rate k, which can be described by a power law of the form τlag ∝  aτ(α) with a sublinear exponent α ≅ 1/2.

Full Text

Duke Authors

Cited Authors

  • Kutsch, M; Hortmann, P; Herrmann, C; Weibels, S; Weingärtner, H

Published Date

  • March 3, 2016

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 019008 -

PubMed ID

  • 26843409

Electronic International Standard Serial Number (EISSN)

  • 1559-4106

International Standard Serial Number (ISSN)

  • 1934-8630

Digital Object Identifier (DOI)

  • 10.1116/1.4941008

Language

  • eng