1 research outputs found
Ionic Strength Effects on Amyloid Formation by Amylin Are a Complicated Interplay among Debye Screening, Ion Selectivity, and Hofmeister Effects
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