Hydroxylated single-walled carbon nanotube inhibits β2m21–31 fibrillization and disrupts pre-formed proto-fibrils

Pathological aggregation of amyloid polypeptides is associated with numerous degenerative diseases. Preventing aggregation and clearing amyloid deposits are considered as promising strategies against amyloidosis. With the capacity of crossing the blood-brain barrier and good biocompatibility, the hydroxylated single-walled carbon nanotube (SWCNT-OH) has been shown with excellent anti-amyloid properties. Here, we systematically studied the SWCNT-OH effects on the fibrillization of the β2m21–31 peptides utilizing all-atom discrete molecular dynamics (DMD) simulation. Our results demonstrated the isolated β2m21–31 peptides first nucleated into unstructured oligomers followed by coil-to-sheet conformational conversions in oligomers with at least six peptides. The elongation and lateral surfaces of the preformed β-sheet could catalyze the other unstructured monomers and small oligomers converted into β-sheet formations via dock-lock fibril growth and secondary nucleation processes. Eventually, the β2m21–31 peptides would self-assemble into well-ordered cross-β structures. Regardless of isolated monomers or well-defined cross-β assemblies, the β2m21–31 would attach on the surfaces of SWCNT-OH adopting unstructured formations indicating the SWCNT-OH not only inhibited the fibrillization of β2m21–31 but also destroyed pre-formed proto-fibrils. Overall, our study displays a complete picture of the fibrillization mechanism of β2m21–31 and the amyloid inhibitory mechanism of SWCNT-OH, offering new insight into the de-novo design of anti-amyloid inhibitors.