Folding, Self-Assembly, and Bulk Material Properties of a De Novo Designed Three-Stranded β-Sheet Hydrogel

Abstract

A de novo designed three-stranded beta-sheet (TSS1) has been prepared that undergoes temperature-induced folding and self-assembly to afford a network of beta-sheet rich fibrils that constitutes a mechanically rigid hydrogel. Circular dichroism and infrared spectroscopies show that TSS1 folds and self-assembles into a beta-sheet secondary structure in response to temperature. Rheological measurements show that the resulting hydrogels are mechanically rigid [at pH 9, G' = 1750-9000 Pa, and at pH 7.4, G' = 8500 Pa] and that the storage modulus can be modulated by temperature and peptide concentration. Nanoscale structure analysis by transmission electron microscopy and small angle neutron scattering indicate that the hydrogel network is comprised of fibrils that are about 3 nm in width, consistent with the width of TSS1 in the folded state. A unique property of the TSS1 hydrogel is its ability to shear-thin into a low viscosity gel upon application of shear stress and immediately recover its mechanical rigidity upon termination of stress. This attribute allows the hydrogel to be delivered via syringe to a target site with spatial and temporal resolution. Finally, experiments employing C3H10t1/2 mesenchymal stem cells seeded onto the hydrogel and incubated for 24 h indicate that the TSS1 hydrogel surface is noncytotoxic, supports cell adhesion, and allows cell migration.

Peptide-based biopolymers in biomedicine and biotechnology

“…Pochan and Schneider have demonstrated that short amphiphilic peptides that fold into β-hairpin structures will self-assemble into injectable hydrogels that can be used for tissue engineering [236][237][238][239][240][241][242][243][244][245]. The 20-amino acid peptide is composed of two sequences of alternating valine and lysine residues, which have a high propensity for β-sheet formation, adjoining a strong β-turn forming tetrapeptide (-V D PPT-).…”

“…The 20-amino acid peptide is composed of two sequences of alternating valine and lysine residues, which have a high propensity for β-sheet formation, adjoining a strong β-turn forming tetrapeptide (-V D PPT-). The molecule is induced into an intramolecularly folded β-hairpin structure by various external stimuli including pH [236], temperature [237], salt [238], and light [240,244]. The alternating valine and lysine residues are oriented such that the molecule is amphiphilic and has one polar, lysine-rich face and one nonpolar, valine-rich face.…”

Gasotransmitter delivery via self-assembling peptides: Treating diseases with natural signaling gases

“…Peptide-based gels are composed of biologically relevant components (amino acids) that are inherently biodegradable and usually non-toxic and non-immunogenic [123]. Additionally, some peptide-based hydrogels are either sheer thinning or gel instantaneously upon injection into the body [124]. These properties allow for syringe injection of materials to a site of interest, avoiding the need for any toxic crosslinkers.…”

Bone Graft Substitutes for Bone Defect Regeneration. A Collective Review

“…Biocompatible and biodegradable [147][148][149][150][151][152]. The changes in mechanical properties imparted by the addition of PDIPF to PCL could have an effect on bone formation, but that effect is cell type dependent [156].…”