ElectricField as a Disaggregating Agent for AmyloidFibrils.

Foldingand aggregation lie on competing reaction pathways in proteins.Altering the occupancy of one pathway is automatically relayed tothe other pathway, leading to a shift in the balance between the twoprocesses. In particular, it is known that the stabilization of thenative state through mutations or solvent alterations is able to haltaggregation. In this work, we explore the feasibility of using externalelectric field as an agent preventing aggregation through the promotionof folding. We use an atomically accurate protein model and computersimulations to investigate folding and aggregation of alanine polypeptidesin electric field of varying strength. The studied peptides are mostlyunstructured in the absence of the field but experience a transitioninto α-helical states when the field is applied. The transitionis accompanied by the disassembly of preseeded stacked β-sheets,which are used as a model of amyloid fibrils, suggesting that electricfield can be employed to control aggregation propensity of intrinsicallydisordered peptides. According to our calculations, the strength ofthe field required for the disaggregation could be suitable for bothcontrolled in vitroexperiments as well as for experimentson live cells. Additionally, our estimates suggest that endogenouselectric fields may have a significant effect on in vivoamyloid formation. [ABSTRACT FROM AUTHOR]