C₃N Nanosheets Inhibit Aβ Dimerization in a Size-Dependent Manner.

Area of Science:

• Biophysics
• Materials Science
• Neuroscience

Background:

• Alzheimer's disease (AD) is a prevalent neurodegenerative disorder.
• Amyloid-beta (Aβ) peptide aggregation, particularly oligomers, is central to AD pathogenesis.
• Two-dimensional (2D) nanomaterials show potential in preventing Aβ oligomerization.

Purpose of the Study:

• To investigate the effect of 2D C3N nanosheet size on Aβ peptide dimerization.
• To understand the molecular mechanisms underlying the interaction between C3N nanosheets and Aβ peptides.
• To explore the potential of size-engineered C3N nanomaterials for AD therapeutic intervention.

Main Methods:

• All-atom molecular dynamics (MD) simulations were employed.
• Systematic investigation of C3N nanosheet sizes (12.6, 6.72, and 0.42 nm²) effects on Aβ dimerization.
• Analyses included structural conformations, PCA, secondary structures, contact probabilities, hydrogen bonding, binding free energies, and binding details.

Main Results:

• A pronounced size-dependent inhibitory effect of C3N nanosheets on Aβ dimerization and β-sheet formation was observed.
• Larger C3N nanosheets (12.6 and 6.72 nm²) effectively suppressed Aβ dimerization and prevented β-sheet structures.
• The smallest C3N nanosheet (0.42 nm²) exhibited negligible inhibition due to limited peptide binding.

Conclusions:

• Larger C3N nanosheets inhibit Aβ aggregation by adsorbing entire peptides, spatially separating them.
• The size of C3N nanosheets is critical for their anti-oligomerization efficacy against Aβ peptides.
• Size-engineered C3N nanomaterials show promise as therapeutic candidates for Alzheimer's disease.