Chiral effect at protein/graphene interface: a bioinspired perspective to understand amyloid formation

Area of Science:

• Biochemistry
• Materials Science
• Neuroscience

Background:

• Protein misfolding into amyloid aggregates is a key factor in neurodegenerative diseases.
• Amyloid formation is linked to molecular surfaces like biological membranes, but the role of surface features like chirality is not well understood.

Purpose of the Study:

• To investigate how surface chirality influences amyloid-beta (Aβ(1-40)) fibril formation.
• To explore the biomimetic role of graphene oxide (GO) surfaces in amyloidogenesis.

Main Methods:

• Utilized cysteine enantiomer modified graphene oxide (GO) as a model system.
• Studied the adsorption, nucleation, and elongation processes of Aβ(1-40) on chiral surfaces.
• Analyzed the conformational changes of Aβ(1-40) using techniques sensitive to secondary structure.

Main Results:

• R-cysteine modified GO suppressed Aβ(1-40) adsorption, nucleation, and elongation, inhibiting fibril formation.
• S-cysteine modified GO promoted these aggregation processes.
• Surface chirality significantly influenced the α-helix to β-sheet conformational transition of Aβ(1-40).
• The chiral effect was dependent on the distance between chiral moieties and the GO surface; a 1-2 nm spacer eliminated the effect.

Conclusions:

• Surface chirality is a critical factor modulating amyloid fibril formation.
• Graphene oxide surfaces play a crucial role in surface-mediated amyloidogenesis.
• Findings provide biomimetic insights into understanding amyloidosis on surfaces and potential therapeutic strategies.