Dilute Self-Healing Hydrogels of Silk-Collagen-Like Block Copolypeptides at Neutral pH

Abstract

We report on self-healing, pH-responsive hydrogels that are entirely protein-based. The protein is a denovo designed recombinant triblock polypeptide of 66 kg/mol consisting of a silk-like middle block (GAGAGAGH)48, flanked by two long collagen-inspired hydrophilic random coil side blocks. The pH-dependent charge on the histidines in the silk block controls folding and stacking of the silk block. At low pH the protein exists as monomers, but above pH 6 it readily self-assembles into long fibers. At higher concentrations the fibers form self-healing physical gels. Optimal gel strength and self-healing are found at a pH of around 7. The modulus of a 2 wt % gel at pH 7 is G' = 1700 Pa. Being protein-based, and amenable to further sequence engineering, we expect that these proteins are promising scaffold materials to be developed for a broad range of biomedical applications.

Controlling supramolecular polymerization through multicomponent self‐assembly

“…384 This observation was attributed to the slow crystallization of the PFS-core in protic polar solvents. 385 Due to the kinetic stability of the cylindrical micelles the Winnik and Manners groups have been able to build increasingly sophisticated superstructures with multiple levels of structural hierarchy, for example the gradient CDSA into cylindrical comicelles with segmented coronas, 386 the self-assembly of the multiblock comicelles into nanofibrillar hydrogels, 387 [394][395][396][397][398][399][400][401] In most of the reported examples these triblocks consist of a central silk inspired [402][403][404][405][406][407][408][409] repeat of (GAGAGAGX) n (where X 5 E, K, or H; n 5 48), which are flanked by two hydrophilic and inert collagen-based blocks that are dimers of the triplet repeat (GXY) n (where X and Y are rich in Q, N, and S; n 5 99) (Fig. 31).…”

“…These were studied in great detail using CD and FT-IR spectroscopy, TEM, cryo-TEM, AFM, SLS, SAXS, and rheometry. 394,[396][397][398]400,401 Intriguingly, the self-assembly was found to take place only on one side of the growing fibrils, and these ends remain reactive if all unimer is consumed [ Fig. 31(c,d)].…”

Reversible Temperature-Switching of Hydrogel Stiffness of Coassembled, Silk-Collagen-Like Hydrogels

“…The production of S H 8 C R 4 T 9 by methanol fed-batch fermentation in 2.5 L Bioflo 3000 bioreactors (New Brunswick Scientific) was as described previously. 26 The purification and characterization of S H 8 C R 4 T 9 is described briefly in the Supporting Information ( Figures S1 and S2). The amino acid sequence of C R 4 and S H 8 C R 4 T 9 can be found in Supporting Information, Figure S3.…”

Development of New Smart Materials and Spinning Systems Inspired by Natural Silks and Their Applications

“…The SELP/DNA complex formed a hydrogel at body temperature and could be used for injectable gene delivery. Cohen Stuart's group designed a series of stimuliresponsive silk collagen-like polypeptides C S C n X 2 2 ( ) composed of a middle silkworm silk-like peptide domain (S) flanked by two collagen-like peptide domains (C) (Martens et al, 2009;Beun et al, 2012Beun et al, , 2014Golinska et al, 2014). The middle silk domains consisted of the sequence GAGAGAGX, and pH-responsive amino residues were introduced at position X, resulting in the pH-triggered self-assembly of C S C n X 2 2 into various nanomaterials (micelles, nanofibers, nanotapes, and hydrogels).…”