Origins of the Superiority of Oscillating Electric Fields for Disrupting Senile Plaques: Insights from the 7-Residue Fragment and the Full-length Aβ-42 Peptide

Surajit Kalita*, David Danovich, Sason Shaik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Our recent molecular dynamics simulations of decomposing Alzheimer’s disease plaques, under oscillating- and static external electric fields (Os-EEFs and St-EEFs), revealed the superiority of Os-EEF for decomposing plaques consisting of the 7-residue peptide segment. This conclusion is now reinforced by studying the dimers of the short peptides and trimers of the full-length Aβ-42 peptide. Thus, the dispersed peptides obtained following St-EEF applications reformed the plaques once the St-EEF subsided. In contrast, plaques originating from the application of Os-EEF remained dispersed for long time scales. The present study provides insights into these results by modeling the decomposition modes that transpire under both field types. Additionally, this study provides insights into the frequency effects on the decomposition processes within the THz-MHz regions. The simulation shows that the Os-EEF in the lower frequency range (≤GHz) decomposes the plaque on a time scale of ∼50 ns, whereas the higher frequency Os-EEFs (≥THz) are less effective. As such, Os-EEFs with moderate-to-low frequencies (≤GHz) lead to an “explosion,” whereby the peptides fly distantly apart and inhibit plaque reformation. By contrast, St-EEFs form parallel peptide pairs, which are stabilized by the EEF due to the large dipole moment of the ensemble. Thus, St-EEF applications lead to sluggish and reversible plaque decomposition processes. We further conclude that the Os-EEF impact is maximal for short pulses, which prevents the EEF propensity to arrange the peptides in parallel pairs. The superiority of the Os-EEF over the St-EEF is maintained irrespective of the peptides’ length. A model is formulated that predicts the dependence of the decomposition time scale on the EEF.

Original languageEnglish
Pages (from-to)2626-2641
Number of pages16
JournalJournal of the American Chemical Society
Volume147
Issue number3
DOIs
StatePublished - 22 Jan 2025

Bibliographical note

Publisher Copyright:
© 2025 The Authors. Published by American Chemical Society.

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