title: Dissecting ion-specific from electrostatic salt effects on amyloid fibrillation: A case study of insulin.
abstract: 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.
authors: Department of Physical Chemistry I, Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors: Miriam
authors: M
authors: Kutsch
authors: Department of Physical Chemistry I, Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors: Pascal
authors: P
authors: Hortmann
authors: Department of Physical Chemistry I, Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors: Christian
authors: C
authors: Herrmann
authors: Department of Physical Chemistry II, Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors: Sebastian
authors: S
authors: Weibels
authors: Department of Physical Chemistry II, Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors: Hermann
authors: H
authors: Weingärtner
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D009994:Osmolar Concentration; D055503:Protein Multimerization; D012492:Salts / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D055672:Static Electricity
chemical_list: D000682:Amyloid; D007328:Insulin; D012492:Salts