Electric field as a disaggregating agent for amyloid fibrils.

Folding and aggregation lie on competing reaction pathways in proteins. Altering the occupancy of one pathway is automatically relayed to the other pathway, leading to a shift in the balance between the two processes. In particular, it is known that the stabilization of the native state through mutations or solvent alterations is able to halt aggregation. In this work, we explore the feasibility of using external electric field as an agent preventing aggregation through the promotion of folding. We use an atomically accurate protein model and computer simulations to investigate folding and aggregation of alanine polypeptides in electric field of varying strength. The studied peptides are mostly unstructured in the absence of the field but experience a transition into α-helical states when the field is applied. The transition is accompanied by the disassembly of preseeded stacked β-sheets, which are used as a model of amyloid fibrils, suggesting that electric field can be employed to control aggregation propensity of intrinsically disordered peptides. According to our calculations, the strength of the field required for the disaggregation could be suitable for both controlled in vitro experiments as well as for experiments on live cells. Additionally, our estimates suggest that endogenous electric fields may have a significant effect on in vivo amyloid formation.