Electromagnetic field modulates aggregation propensity of amyloid peptides.

Nonthermal effects of the electromagnetic (EM) field in the radio and microwave frequency ranges on basic biological matter are difficult to detect and thus remain poorly understood. In this work, all-atom nonequilibrium molecular dynamics simulations were performed to investigate the molecular mechanisms of an amyloidogenic peptide response to nonionizing radiation of varying field characteristics. The results showed that the EM field induced peptide conformations dependent on the field frequency and strength. At the high field strength (0.7 V/nmrms), the peptide explored a wider conformational space as the frequency increased from 1.0 to 5.0 GHz. At the intermediate strength fields (0.07-0.0385 V/nmrms), the frequencies of 1.0 and 2.5 GHz resulted in the peptide being trapped in specific conformations, with 1.0 GHz enabling both fibril-forming and fibril-inhibiting conformations, while 2.5 GHz led to formation of mostly fibril-forming conformations. In contrast, the 5.0 GHz frequency caused increased peptide dynamics and more extended conformations with fibril-enabling aromatic side-chain arrangement akin to the structures formed under ambient conditions. All the simulated frequencies at low strength fields (0.007-0.0007 V/nmrms) resulted in the formation of amyloid-prone hairpin conformations similar to those formed under the weak static electric field and ambient conditions. These results suggest that specific ranges of EM field parameters produce peptide conformations unfavorable for formation of amyloid fibrils, a phenomenon that can be exploited in treatment and prevention of amyloid diseases. Alternatively, EM field parameters can be selected to modulate the formation of well-ordered peptide assemblies as a rational design strategy for engineering biocompatible materials.