Title : The amyloidogenic peptide stretch in human tau, tau306–311 is a promising injectable hydrogelator
Abstract:
A vast majority of peptide hydrogelators harbor a bulky, non-native aromatic moiety such as fluorene and naphthalene. These moieties facilitate self-assembly through stacking interactions and therefore serve as self-assembly platforms for hydrogels. Incorporation of foreign aromatic moieties, however, raises safety concerns as far as biomedical applications are concerned. The hydrogel research, therefore, has branched to another dimension to identify native or native-like short peptide stretches that could cause the gelation of biological fluids. For instance, the degradation of Fmoc-FF hydrogel causes cell death through necrosis. The following three criteria were applied to shortlist the peptides: (i) the peptide has one or more charged residues, (ii) there is at least one aromatic residue, and (iii) the peptide selfassembles through parallel β-sheet formation, preferably the in-register β-sheet. Using well-defined criteria, we identified the hexapeptide stretch from human tau, viz. tau306–311 (Ac-PHF6), as a promising injectable hydrogelator. Ac-PHF6 caused instant gelation of PBS at the concentration of 20 mM. The high quantum yield observed in ThT fluorescence assay indicated the formation of amyloid-like fibrils. Structural analysis using CD and FTIR spectroscopy confirmed the presence of β-sheet secondary structures in the saline environment. TEM images of hydrogel revealed the formation of long, straight fibrillar networks. The hydrogel demonstrated excellent biocompatibility by supporting the growth of HEK-293 cells. Additionally, it exhibited sustained release for both doxorubicin and calcein. Ac-PHF6 hydrogel stability assay shows that at least 95 % of peptide remains inside the hydrogel for up to two weeks. This is a valuable attribute of a wound-dressing material that can keep the wound moist, supporting regular cellular activity and promoting healing. Such hydrogels find applications as drug delivery vehicles, scaffolds for mammalian cell culture, wound-dressing material, etc.
