Aptamer as a Tool for Investigating the Effects of Electric Field on Aβ₄₀ Monomer and Aggregates Using...

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.