Cross-fibrillation of insulin and amyloid β on chiral surfaces: Chirality affects aggregation kinetics and cytotoxicity

Recent clinical and epidemiological research has shown that insulin is associated with the pathological mechanisms of Alzheimer's disease (AD) and can protect against the oxidative stress triggered by amyloid-β peptide (Aβ). Herein, we present a systematic study on how the cross-fibrillation of insulin and Aβ is influenced by the surface chirality of an interface designed to mimic their aggregation on the cytomembrane. Intriguingly, the surface chirality strongly affected the aggregation kinetics, structure, morphology, and cellular responses of the cross-aggregates of insulin and Aβ. On a D-phenylalanine-modified surface, Aβ induced insulin to co-aggregate into β-sheet-rich fibrils and cross-fibrils that showed a pronounced cellular toxicity. However, on an L-phenylalanine-modified surface, insulin and Aβ formed non-toxic amorphous aggregates. Our work indicates that surface chirality can influence the cross-fibrillation of Aβ and insulin as well as the cytotoxicity of their aggregates.