De Novo Design of Strand-Swapped β-Hairpin Hydrogels

Abstract

De novo designed peptides, capable of undergoing a thermally triggered beta-strand-swapped self-assembly event leading to hydrogel formation were prepared. Strand-swapping peptide 1 (SSP1) incorporates an exchangeable beta-strand domain composed of eight residues appended to a nonexchangeable beta-hairpin domain. CD shows that, at pH 9 and temperatures less than 35 degrees C, this peptide adopts a random coil conformation, rendering it soluble in aqueous solution. On heating to 37 degrees C or greater, SSP1 adopts a beta-hairpin that displays an exchangeable beta-strand region. The exchangeable strand domain participates in swapping with the exchangeable domain of another peptide, affording a strand-swapped dimer. These dimers further assemble into fibrils that define the hydrogel. A second peptide (SSP2) containing an exchangeable strand composed of only four residues was also studied. Microscopy and scattering data show that the length of the exchangeable domain directly influences the fibril nanostructure and can be used as a design element to construct either twisted (SSP1) or nontwisted (SSP2) fibril morphologies. CD, FTIR, and WAXS confirm that both peptides adopt beta-sheet secondary structure when assembled into fibrils. Fibril dimensions, as measured by TEM, AFM, and SANS indicate a fibril diameter of 6.4 nm, a height of 6.0 nm, and a pitch of 50.4 nm for the twisted SSP1 fibrils. The nontwisted SSP2 fibrils are 6.2 nm in diameter and 2.5 nm in height. Oscillatory rheology, used to measure bulk hydrogel rigidity, showed that the gel composed of the nontwisted fibrils is more mechanically rigid (517 Pa at 6 rad/s) than the gel composed of twisted fibrils (367 Pa at 6 rad/s). This work demonstrates that beta-strand-swapping can be used to fabricate biomaterials with tunable fibril nanostructure and bulk hydrogel rheological properties.

Hydrogels with self-assembling ordered structures and their functions

“…We introduce here one particular type of amphiphiles, artifi cial proteins and carbohydrates, and the resultant supramolecular hydrogels that have been studied intensively. Several research groups are active in designing peptides of charged groups of various lengths as hydrophilic heads and hydrophobic tails [40][41][42][43][44]. After speci fi c stimuli triggers, peptides self-assemble to form a secondary structural motif, such as an α-helix, β-hairpin or even extended fi brils of hydrogels.…”

Design of Self-Assembling Peptides and Their Biomedical Applications

“…These b-sheet peptide nanostructures have been evaluated for the treatment of enamel decay and as an injectable joint lubricant for the treatment of osteoarthritis [81,82]. n b-hairpin peptides b-hairpin peptides are another type of peptide designed by Schneider and colleagues that captures the self-assembling potential afforded by the b-sheet and is prepared from monomers of alternating hydrophilic and hydrophobic residues, lysine and valine, respectively, flanking an intermittent tetrapetide designed to mimic a Type II' b-turn, termed a b-hairpin peptide [83][84][85][86][87]. These peptides are designed to be hydrated in pure water, adopting a random coil conformation.…”

Effect of Helical Flanking Sequences on the Morphology of Polyglutamine-Containing Fibrils

“…This variation in surface-dependent deposition orientation of cross-β-strand fibrils has been observed by others. 23 The morphological features described here for KKQ 25 KK will be compared to related features identified for ecK-Ω-Q 25 KK in the Discussion section.…”