β-Amyloid Targeting with Two-Dimensional Covalent Organic Frameworks: Multi-Scale In-Silico Dissection of Nano-Biointerface

Cytotoxic aggregation of misfolded beta-amyloid (A beta) proteins is the main culprit suspected to be behind the development of Alzheimer's disease (AD). In this study, A beta interactions with the novel two-dimensional (2D) covalent organic frameworks (COFs) as therapeutic options for avoiding beta-amyloid aggregation have been investigated. The results from multi-scale atomistic simulations suggest that amine-functionalized COFs with a large surface area (more than 1000 m(2)/gr) have the potential to prevent A beta aggregation. Gibb's free energy analysis confirmed that COFs could prevent protofibril self-assembly in addition to inhibiting beta-amyloid aggregation. Additionally, it was observed that the amine functional group and high contact area could improve the inhibitory effect of COFs on A beta aggregation and enhance the diffusivity of COFs through the blood-brain barrier (BBB). In addition, microsecond coarse-grained (CG) simulations with three hundred amyloids reveal that the presence of COFs creates instability in the structure of amyloids and consequently prevents the fibrillation. These results suggest promising applications of engineered COFs in the treatment of AD and provide a new perspective on future experimental research.

Automated summary

The study suggests that amine-functionalized COFs have the potential to prevent Aβ aggregation and enhance diffusivity through the BBB. Microsecond CG simulations show that COFs create structural instability in amyloids and prevent fibrillation. These findings highlight the promising applications of engineered COFs in AD treatment and provide a new perspective for future experimental research.