Aptamer as a Tool for Investigating the Effects of Electric Field on Aβ40 Monomer and Aggregates Using Single-Molecule Force Spectroscopy.

The effects of electric field (EF) on amyloid proteins have been given increasing attention in regulation of amyloid-β (Aβ) aggregation and therapeutic methods because of prevalence of Alzheimer's disease. Herein, for the first time, aptamer was used as a tool for investigating the effects of EF on Aβ40 monomer and Aβ40 aggregates (Aβ40 oligomer and Aβ40 fibril) by single-molecule force spectroscopy. Interestingly, EF had different effects on Aβ40 monomer and Aβ40 aggregates, which might be due to the interactions of aptamer with EF-treated Aβ40 monomer and Aβ40 aggregates. With application of EF to Aβ40 oligomer, specific interaction and binding probability of aptamer-Aβ40 oligomer slightly increased. However, the interactions of aptamer with Aβ40 monomer and Aβ40 fibril changed greatly when EF was respectively applied to Aβ40 monomer and Aβ40 fibril. Meanwhile, the interaction of aptamer with Aβ40 monomer changed from nonspecific binding to specific binding. And the rupture force distribution of aptamer-Aβ40 fibril changed from bimodal distribution to unimodal distribution. Hence, it was presumed that Aβ40 oligomer almost maintained oligomeric structure, while Aβ40 fibril and Aβ40 monomer changed into Aβ40 oligomer when EF was applied. Subsequently, this presumption was mainly verified by atomic force microscopy imaging and circular dichroism. This work testifies that aptamer may be a valuable tool to investigate effects of EF on Aβ40 monomer and Aβ40 aggregates. Moreover, the established method provides a new perspective to study aggregation of amyloid proteins.