Amyloid formation of mutated Alzheimer's Aβ 16–36 residues peptide and application in toxic lead and uranium ion binding

Abstract

Amyloid nanostructures are gaining attention as bio-compatible materials with diverse potential applications. The formation/self-assembly of amyloid fibrils, though implicated in the prognosis of several neurodegenerative diseases, contrastingly can also be explored for their functional properties owing to their unique stability and strength. The physicochemical environment and amino-acid composition are characteristic and specifically crucial for a protein/peptide to form amyloid fibrils. The Aβ peptide involved in the Alzheimer's disease prognosis consists of two central hydrophobic core regions and a central polar region forming a β-hairpin. In this study, a 21 amino acid containing peptide KLVFFAEDVESNRGAIIGLMV is designed introducing point mutations to the original 16–36 residues of the Aβ peptide (G → E at position 25 and K → R at position 28), resulting in a modified Aβ peptide variant. The self-assembling nature of this modified peptide has been explored, and ThT fluorescence and circular dichroism spectroscopy exhibit β-sheet structures. Detailed morphological analysis using SEM, AFM, and confocal microscopy revealed a progression from initial blob-like spongy forms to protofibrils, culminating in branched amyloid fibrils. These strategic mutations enable binding of toxic metals such as uranium and lead, as demonstrated via UV-visible spectroscopy, XPS, AAS and fluorescence spectroscopy, highlighting its promise for environmental remediation.