Light-Triggered Disassembly of Amyloid Fibrils

Abstract

There is growing demand for novel methods that could render controlled disassembly of higher-order structures formed, for example, by peptides. Herein, we demonstrate such a method based on the application of a photocaged variant of the amino acid lysine, namely lys(Nvoc). Specifically, we introduce lys(Nvoc) into the primary sequence of the amyloidogenic peptide, Aβ16-22, at a position where the native sidechain is known to play a key role in fibril formation via hydrophobic interactions. Both AFM and infrared spectroscopic measurements indicate that the resultant Aβ16-22 mutant is able to form fibrils; whereas, more importantly, the fibrils thus formed can be completely disassembled upon irradiation with near-UV light, which cleaves the photolabile Nvoc moiety and triggers the restoration of the lysine sidechain. These results suggest that the generation of a single charge in a highly hydrophobic region of the fibrils is sufficient to promote their dissociation. Thus, we envisage that the current approach will find useful applications wherein controlled structural disassembly or content release is required.

Possible Existence of α-Sheets in the Amyloid Fibrils Formed by a TTR105–115 Mutant

“…39,43 As shown (Figure S13 in SI), in the presence of TTR-111D M peptide, the ThT fluorescence intensity is significantly increased, indicating of ThT binding to fibrils; however, the same solution does not show any appreciable ICD signals (Figure S13 in SI). In agreement with Loksztejn et al 43 fibrils with periodic twists such as an Aβ 16–22 derivative, Aβ 16–22 F19K*, 44 was also found to have an observable ICD signal (Figure S14 in SI). Thus, this result corroborates the notion that TTR-111D M forms fibrils without long-range twists.…”

Ultrasound-facilitated assembly and disassembly of a pH-sensitive self-assembly peptide

“…22 The central b-sheet region (LVFFA) of K3C6SPD is derived from amyloid b-peptide, and two phenylalanine (F) residues are critical to the peptide assembly. [23][24][25] Therefore, by the substitution of F20 with histidine (called F20H) (Fig. 1), we extended our previous study and have investigated the separate and combined effect of pH and ultrasound on the assembly and disassembly behaviours of K3C6SPD and F20H.…”

Integrating Mechanical and Biological Control of Cell Proliferation Through Bioinspired Multieffector Materials

“…al have provided evidence of how a simple substitution of lysines by a photocaged variant lys(Nvoc) allows the generation of amyloid fibrils with the capacity of disassembly upon irradiation with UV light. The lysNvoc light-mediated cleavage release the moiety attached to the side chain, restoring the regular amino acid properties and providing a significant change in the hydrophobicity that causes the disassembly of the amyloid fibril (124) .…”