Vibrational circular dichroism sheds new light on the competitive effects of crowding and β-synuclein on the fibrillation process of α-synuclein

The effects of crowding, using the crowding agent Ficoll 70, and the presence of beta-synuclein on the fibrillation process of alpha-synuclein were studied by spectroscopic techniques, transmission electron microscopy and ThT-assays. This combined approach, where all techniques were applied to the same original sample, generated an unprecedented understanding of the effects of these modifying agents on the morphological properties of the fibrils. Separately, crowding gives rise to shorter mutually aligned fibrils while beta-synuclein leads to branched, short fibrils. The combi-nation of both effects leads to short, branched, mutually aligned fibrils. Moreover, it is shown that the non-destructive technique of vibrational circular dichroism is extremely sensitive towards the length and the higher order morphology of the fibrils.