A Class of Ultrasmall Aliphatic Peptides Mimics Natural Fibrous Scaffolds by Self-Assembly

Abstract

A class of ultrasmall tri to hepta peptides self-assemble into hydrogels, due to their characteristic sequence motif - an aliphatic amino acid tail of decreasing hydrophobicity capped by a polar head. These peptides organize themselves to supramolecular scaffolds of long helical fibers that extend to the μm-range. During self-assembly, these peptides form amyloid aggregates via unexpected α-helical intermediates, with the trimer as the shortest ever reported sequence with α-helical propensities. Circular dichroism and X-ray diffraction confirmed conformational changes terminating in thermo-stable β-type structures. Molecular dynamics simulations of peptide behavior in water revealed monomer antiparallel pairing and stably condensed coiled fibers. The assembled macrostructures are biocompatible and non-toxic. Their high mechanical strength can be tuned by adjusting salt and pH, paving the way for applications from injectable therapies to repair and replacement of damaged tissues. In particular, their biocompatibility towards a variety of human and other mammalian primary cells, qualifies them for future applications in tissue engineering and medical regenerative therapy. The ultrasmall size and the dynamic facile assembly process make this peptide class an excellent model system for studying the mechanism of amyloidogenesis, its evolution and pathogenicity.View Large Image | View Hi-Res Image | Download PowerPoint Slide