title: 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.
abstract: 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.
authors: Instituto de Desarrollo Tecnológico para la Industria Química (INTEC), Universidad Nacional del Litoral (UNL), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Santa Fe, Argentina.
authors: Julio A
authors: JA
authors: Deiber
authors: Maria V
authors: MV
authors: Piaggio
authors: Marta B
authors: MB
authors: Peirotti
mesh_terms: D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000737:chemistry*; D055664:Electrochemical Techniques; D019075:Electrophoresis, Capillary; D057446:Hydrodynamics; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D055672:Static Electricity
chemical_list: D016229:Amyloid beta-Peptides; D066329:Protein Aggregates
keywords: Aggregation rates; Amyloid-beta; Electrokinetic properties; Electrophoretic mobility; Hydrodynamic properties