Amytracker shines a light on catalytic amyloids

In addition to their role in neurodegenerative diseases, amyloid fibrils can also catalyse enzymatic reactions. A recent study has shown that bacteria make use of such catalytic amyloids to hydrolyse β-lactam antibiotics. In the present study, Bhaumik et al. develop a catalytic amyloid system which can be turned on and off through irradiation with light.

The amyloidogenic peptide used by the researchers consists of alternating lysine/phenylalanines (“PFK”) which do not spontaneously assemble into amyloid fibrils due to electrostatic repulsion between the amino acid sidechains. However, when the PFK peptide is combined with a merocyanine photoswitch (“MCH”) and irradiated with white light, MCH is transformed into SP and large amyloid fibrils with a parallel orientation are formed. Once the light is turned off, the fibrils quickly fall apart again. Bhaumik and colleagues used Amytracker 680 to effectively detect PFK fibrils and allowed them to follow the assembly and disassembly over time, as well as find optimal PFK:MCH ratios to maximise fibril formation.

Amytracker was also used to show how different moieties of the photoswitch affect fibril formation by comparing the emission kinetics of fibrils formed with SP versus an SP analogue. Together with the results of other physicochemical analyses, the authors concluded that a combination of π-π interactions between SP’s spiropyran moiety and the phenylalanine residues of PFK, as well as electrostatic interactions between the sulfonate moiety of SP and the lysine residues of PFK, explain the rapid formation of macroscopic PFK:MCH fibrils upon irradiation. Finally, the authors showed that the light-induced PFK:MCH amyloid fibrils are able to catalyse the hydrolysis of β lactams nitrocefin and penicillin G. Just as the amyloid fibril formation, the catalytic activity could be turned on and off through illumination with light.

Taken together, the authors developed a novel catalytically competent and reversible amyloid system controlled by a light-sensing small molecule. The authors point out that the tunable ability to effectively hydrolyse β-lactams could have future applications in water treatment through removal of antibiotics.

Image:Amytracker detects formation of photo-switched amyloid fibrils. Top: Light-activated assembly of amyloidogenic peptides (squiggly lines) and photo-switch small molecule (blue circles) into catalytically active fibrils. Bottom: i) Amytracker 680 fluorescence spectra for different peptide:photo-switch molar ratios. ii) Time-dependent Amytracker fluorescence before, during and after light irradiation. Adapted from Figure 1, 2, Bhaumik et al. 2026 (CC BY 4.0)..