Charge regulation phenomenon predicted from the modeling of polypeptide electrophoretic mobilities as a relevant mechanism of amyloid-beta peptide oligomerization

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

ELECTROPHORESIS

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2016 vol. 37 p. 711 - 718

0173-0835

Electrophoretic mobilities of amyloid-beta (1-40) and (1-42) peptides and their aggregates are modeled to study the amyloidogenic pathway associated with Alzheimer´s Disease. The near molecule pH generated by the intraparticle charge regulation phenomenon during the oligomerization of amyloid-beta (1-40) and (1-42) peptides is evaluated and discussed as a relevant mechanism supporting the amyloid cascade hypothesis proposed in the literature. A theoretical framework associated with the oligomerization of amyloid beta peptides including simple scaling laws and the consideration of electrokinetic and hydrodynamic global properties of oligomers is presented. The central finding is the explanation of the near molecule pH change toward the pI when the oligomerization number increases. These results allow one to rationalize consecutive physical stages that validate the amyloid cascade hypothesis. Concluding remarks involving mainly the effects of pair and intraparticle charge regulation phenomena on the amyloidogenic pathway with somes uggestions for future research are provided.