The rationales that researchers utilize today for functional peptide design are mostly derived from the natural protein and peptide investigations. Indeed, some naturally occurring peptides can be pathology related. In Alzheimer’s disease, there is a critical motif LVFFA (Aβ_{17- 21}) in the amyloid-beta (Aβ) peptide, which is responsible for peptide monomer self-assembly to form oligomers and fibrils. A previous report about peptide and plasmid DNA co-assembly for gene delivery has made use of this segment, Aβ_17-21 to design a peptide/plasmid nanostructure. However, putatively, Aβ_17-21 in that peptide has caused the peptide/plasmid particle to form an overly robust structure and incapacitated gene release and expression. In this report, the focus is therefore put on controlling th...[ Read more ]

The rationales that researchers utilize today for functional peptide design are mostly derived from the natural protein and peptide investigations. Indeed, some naturally occurring peptides can be pathology related. In Alzheimer’s disease, there is a critical motif LVFFA (Aβ_{17- 21}) in the amyloid-beta (Aβ) peptide, which is responsible for peptide monomer self-assembly to form oligomers and fibrils. A previous report about peptide and plasmid DNA co-assembly for gene delivery has made use of this segment, Aβ_17-21 to design a peptide/plasmid nanostructure. However, putatively, Aβ_17-21 in that peptide has caused the peptide/plasmid particle to form an overly robust structure and incapacitated gene release and expression. In this report, the focus is therefore put on controlling the fibrillation behavior of the Aβ_17-21 modulated self-assembling peptide. Aβ_17-21, apart from its strongly associative structure, is relatively insensitive to pH. Therefore, we incorporated the self-assembling motif with pH-sensitive histidine. Results showed that with histidine-substitution, the fibrillation propensity and structural robustness of peptide assembly are lowered and the pH-sensitivity is higher. Meanwhile, bifurcation characteristics and fibrillar height range are retained due to the sequence similarity. In addition, ultrasound was applied to accelerate both fibril formation and disruption at different pH conditions. The accelerative effect can act as a compensation for the slowed fibrillation process. The findings have given an insight into the natural peptide motif mutation study, demonstrating that the peptide functionality can be adjusted and desired triggers can be incorporated.