Stimuli responsive fibrous hydrogels from hierarchical self-assembly of a triblock copolypeptide

Abstract

In this work, the self-assembly behavior and pH responsiveness of a triblock copolypeptide in aqueous media are demonstrated. The copolypeptide was composed of a central pH responsive poly(l-glutamic acid) (PGA), flanked by two hydrophobic poly(l-alanine) blocks (PAla) (PAla5-PGA11-PAla5). This system showed a pH-responsive transition from short tapes to spherical aggregates by increasing the pH, as a result of deprotonation of the PGA block and a conformational change from α-helix to random coil. Increasing the ionic strength to physiological conditions (0.15 M) has triggered fibrillar self-assembly through intermolecular hydrogen bonding of PAla end-blocks that form β-sheet nanostructures, in conjunction with charge screening of the central random coil PGA segments. At elevated concentrations a thermo-responsive free supporting hydrogel was obtained, consisting of rigid β-sheet based twisted superfibers, resulting from hierarchical self-assembly of the copolypeptide. Yet, morphological transformation of this nanostructure was observed upon switching the pH from physiological conditions to pH 4. An unexpected morphology constituted of α-helix-based giant nanobelts was observed as a consequence of the secondary peptide transitions.

Injectable Hydrogel: Amplifying the pH Sensitivity of a Triblock Copolypeptide by Conjugating the N-Termini via Dynamic Covalent Bonding

“…denaturation upon heating). As we have shown previously, 43 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 8 solutions underwent a sol-gel transition after heating and slow cooling thermal treatment, forming opaque stiff gels. Structural investigation by electron microscopy (TEM and SEM) revealed that the copolypeptide chains underwent hierarchical growth of β-sheet-based fibrils, into giant bundles of superfibers that were disrupted and rearranged upon thermal treatment into a supermolecular network of twisted rigid superfibers ( Figure 1).…”

“…We have studied the aqueous self-assembly behavior of a benzaldehyde endcapped poly(L-alanine)-b-poly(L-glutamic acid)-b-poly(L-alanine), triblock copolypeptide (Bz-A 5 E 11 A 5 -Bz), As previously reported, 43 at physiological pH and ionic strength (7.4, 0.15M NaCl) and elevated concentrations, the bare triblock copolypeptide underwent hierarchical growth of fibrils into giant supermolecular tapes that could be disrupted and rearranged into a supermolecular network of twisted fibers upon temperature treatment. In the following, the N-termini of the triblock copolypeptide, were end-capped by benzaldehyde (Bz) through dynamic imine bond.…”

“…This result is in line 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 13 with the concentration dependence of the gelation temperature. 43 Hence, we have considered increasing the fraction of the thin superfibers by mixing conjugated and bare copolypeptides in order to attempt tuning the gelation window. For this purpose, a mixture of triblock copolypeptide with its Bz conjugate at 50/50 weight ratio, was investigated in 10 wt% overall polymer concentration aqueous solution of pH 6.5. of the isolated superfibers (versus stacked), seems to be the determining factor affecting the overall elasticity of the hydrogel.…”

NIPAm-Based Modification of Poly(L-lysine): A pH-Dependent LCST-Type Thermo-Responsive Biodegradable Polymer

“…The thermo-induced formation of the transparent gel observed in Figure 2 A is attributed to the α -helix-to- β -sheet transformation of the majority of the PLL chains, associated with the formation of a spanning 3D physical network. As reported, the peptides, when adopting a β -sheet secondary structure, self-assemble, forming entangled fibrils, which justifies the gel appearance [ 24 ]. The transition temperature was detected at about 45 °C, which seems reasonable for the molecular weight of PLL (Mn = 6500), as it is known that it depends on PLL molecular weight [ 25 ].…”

Extremely Stable Supramolecular Hydrogels Assembled from Nonionic Peptide Amphiphiles

“…Hydrogels offer great potential for applications in biomaterials like three-dimensional (3D) scaffolds, − drug delivery carriers, , and surgical dressings . In particular, a peptide hydrogel is an outstanding candidate because of its good biocompatibility, biodegradability, and versatile biofunctionalization. − A peptide hydrogel can be easily obtained from natural peptides with a specific sequence like fibrin, collagen, and de novo-designed short peptides − and peptide amphiphiles (PAs). − However, natural peptide hydrogels have limitations such as deficient diversity, limited sources, large batch heterogeneity, and the inherent presence of water-soluble residuals. In particular, synthetic peptide hydrogels based on PAs offer more advantages in versatility, stability, and processing feasibility.…”