Electric field as a disaggregating agent for amyloid fibrils

Area of Science:

• Biophysics
• Computational Biology
• Protein Science

Background:

• Protein folding and aggregation are competing processes influencing protein function and disease.
• Stabilizing native protein states can inhibit aggregation, but alternative methods are sought.
• Amyloid fibrils, implicated in neurodegenerative diseases, form through protein aggregation.

Purpose of the Study:

• To investigate the potential of external electric fields to control protein aggregation.
• To explore electric field-induced protein folding and its effect on pre-existing aggregates.
• To assess the feasibility of using electric fields for therapeutic interventions against protein aggregation.

Main Methods:

• Atomically accurate protein model and computer simulations were employed.
• Alanine polypeptides were simulated under varying electric field strengths.
• The study focused on the transition between unstructured states, α-helical structures, and β-sheet disassembly.

Main Results:

• In the absence of an electric field, polypeptides were largely unstructured.
• Application of electric fields induced a transition to α-helical states.
• Preseeded stacked β-sheets, modeling amyloid fibrils, were disassembled by the electric field.

Conclusions:

• External electric fields can prevent protein aggregation by promoting folding.
• The electric field strengths required are potentially suitable for in vitro and in vivo applications.
• Endogenous electric fields may play a significant role in in vivo amyloid formation.