Fluorination induced inversion of helicity and self-assembly into cross-α like piezoelectric amyloids by minimalistic designer peptide

Although initially identified as pathological aggregates, amyloid fibrillar assemblies formed by various proteins and peptides are now known to have crucial physiological roles, carrying out numerous biological functions in almost all organisms. Due to unique features, the common etiology of amyloids’ cross-𝜷 structure is long posited as a template for designing artificial self-assembling systems. However, the recent discovery of cross-𝜶 amyloids indicates additional structural paradigms for self-assembly into ordered nanostructures, turning significant attention toward designing artificial nanostructures based on cross-𝜶 assembly. Herein, a minimalistic designer peptide which forms a hydrogen-bonded amyloid-like structure while remaining in the 𝜶 region of conformation is engineered, to investigate the effect of aromatic, hydrophobic, and steric considerations on amyloidal assemblies. These results demonstrate a significant modulation of helicity and self-assembly, leading to the structure-dependent piezoelectric function of the amyloid-like cross-𝜶 fibrils. This study indicates a potential avenue for molecular engineering of functional peptide materials.