Amyloid fibrils for the construction of functional materials

Amyloid aggregates, which were historically associated with diseases, represent a highly promising class of safe and sustainable biomaterials, suitable for both in vitro and in vivo applications. Amyloids consist of peptide monomers that self-assemble into nanofibrils with b-type structures [1]. Their unique properties at the nanoscale include high mechanical strength, biocompatibility, biodegradability as well as thermal and chemical stability. Moreover, amyloid assemblies can orthogonally functionalized with a wide range of biomolecules, such as enzymes and large proteins [2]. This would lead to the development of multifunctional nanomaterials suitable for the construction of complex devices acting as biosensors, drug delivery systems and catalysts for complex syntheses. In this context, we are developing nanofibrils based on natural and de novo designed peptides as a “proof of principle” strategy for the construction of functional nanomaterials. TTR105-115 peptide, a fragment of human transthyretin, has been selected as the self-assembling sequence. The resulting fibrils have been covalently functionalized with a synthetic mini-peroxidase (FeMC6*a) using the strain-promoted azide-alkyne cycloaddition click chemistry (SPAAC, Figure 1). The resulting bionanoconjugate has been thoroughly characterized by means of several techniques, such as mass spectrometry, transmission electron microscopy and circular dichroism. The catalytic properties of the resulting nanomaterial will be evaluated using model oxidation reactions. This work aims at showing that the resulting nanomaterial retains the catalytic properties of the artificial metalloprotein FeMC6*a, while preserving its amyloid nanostructure. This strategy will open new opportunities for the development of innovative materials with applications in biosensing and biocatalysis. [1] R. Hjorth, L. van Hove, and F. Wickson, Nanotoxicology, 11 (2017) 305–312. [2] S. Al-Halifa, M. Babych, X. Zottig, D. Archambault, and S. Bourgault, Peptide Science, 111 (2019).