Estimation of electrokinetic and hydrodynamic global properties of relevant amyloid-beta peptides through the modeling of their effective electrophoretic mobilities and analysis of their propensities to aggregation

JULIO A. DEIBER; MARÍA V. PIAGGIO; MARTA B. PEIROTTI

JOURNAL OF SEPARATION SCIENCE

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2014 vol. 37 p. 2618 - 2624

1615-9306

Neuronal activity loss may be due to toxicity caused by amyloid-beta peptides forming soluble oligomers. Here amyloid-beta peptides (1?42, 1?40, 1?39, 1?38, and 1?37) are characterized through the modeling of their experimental effective electrophoretic mobilities determined by a capillary zone electrophoresis method as reported in the literature. The resulting electrokinetic and hydrodynamic global properties are used to evaluate amyloid-beta peptide propensities to aggregation through pair particles interaction potentials and Brownian aggregation kinetic theories. Two background electrolytes are considered at 25°C, one for pH 9 and ionic strength I= 40 mM (aggregation is inhibited through NH4OH) the other for pH 10 and I= 100 mM (without NH4OH). Physical explanations of peptide oligomerization mechanisms are provided. The effect of hydration, electrostatic, and dispersion forces in the amyloidogenic process of amyloid-beta peptides (1?40 and 1?42) are quantitatively presented. The interplay among effective charge number, hydration, and conformation of chains is described. It is shown that amyloid-beta peptides (1?40 and 1?42) at pH 10, I= 100 mM and 25°C, may form soluble oligomers, mainly of order 2 and 4, after an incubation of 48 h, which at higher times evolve and end up in complex structures (protofibrils and fibrils) found in plaques associated with Alzheimer's disease.