Conformation Control of Amyloid Filaments by Repeated Thermal Perturbation

We report that repeated thermal perturbation by thermal cycling (TC) accelerates the formation rate of amyloid filaments at microliter volumes (10-200 mu L) and produces a new conformation of zigzag-shaped filaments. The amyloid filaments have been synthesized under different TC conditions, such as temperature variations (Delta T = 0-86 degrees C) and the number of cycles (C# = 30-90). In particular, the filament formation was promoted by TC with Delta T >= 30 degrees C. This indicates that the change in binding energy of beta-sheets and the breakage of disulfide bonds induced by TC with large Delta T contributed to the increased filament growth. This molecular interaction was investigated by molecular dynamics simulation. We also found that TC leads to the formation of amyloid filaments with peculiar conformation (zigzag-shaped filaments). Moreover, key structural parameters (tortuosity, segment length, and joint angle) of the amyloid filaments could be fine-tuned by selecting certain Delta T conditions. Taken together, we confirmed that the TC not only promotes the formation of amyloid filaments but also affects the conformational changes of the filaments.

Automated summary

The study revealed that repeated thermal perturbation by thermal cycling accelerates the formation rate of amyloid filaments at microliter volumes and produces a new conformation of zigzag-shaped filaments. Specific thermal cycling conditions promote filament formation, and the key structural parameters of filaments can be fine-tuned by selecting different temperature variations.