title: Ionic strength effects on amyloid formation by amylin are a complicated interplay among Debye screening, ion selectivity, and Hofmeister effects.
abstract: Amyloid formation plays a role in a wide range of human diseases. The rate and extent of amyloid formation depend on solution conditions, including pH and ionic strength. Amyloid fibrils often adopt structures with parallel, in-register β-sheets, which generate quasi-infinite arrays of aligned side chains. These arrangements can lead to significant electrostatic interactions between adjacent polypeptide chains. The effect of ionic strength and ion composition on the kinetics of amyloid formation by islet amyloid polypeptide (IAPP) is examined. IAPP is a basic 37-residue polypeptide responsible for islet amyloid formation in type 2 diabetes. Poisson-Boltzmann calculations revealed significant electrostatic repulsion in a model of the IAPP fibrillar state. The kinetics of IAPP amyloid formation are strongly dependent on ionic strength, varying by a factor of >10 over the range of 20-600 mM NaCl at pH 8.0, but the effect is not entirely due to Debye screening. At low ionic strengths, the rate depends strongly on the identity of the anion, varying by a factor of nearly 4, and scales with the electroselectivity series, implicating anion binding. At high ionic strengths, the rate varies by only 8% and scales with the Hofmeister series. At intermediate ionic strengths, no clear trend is detected, likely because of the convolution of different effects. The effects of salts on the growth phase and lag phase of IAPP amyloid formation are strongly correlated. At pH 5.5, where the net charge on IAPP is higher, the effect of different anions scales with the electroselectivity series at all salt concentrations.
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Marek
authors.forename: Vadim
authors.initials: V
authors.lastname: Patsalo
authors.forename: David F
authors.initials: DF
authors.lastname: Green
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Raleigh
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007477:Ions / Q000737:chemistry / Q000378:metabolism; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009994:Osmolar Concentration
chemical_list: D000682:Amyloid; D007477:Ions; D058228:Islet Amyloid Polypeptide