Tunable mechano-responsive organogels by ring-opening copolymerizations of N-carboxyanhydrides

Abstract

The simple copolymerization of N-carboxyanhydride (NCA) monomers is utilized to generate copolypeptides having a combination of α-helix and β-sheet sub-structures that, when grown from a solvophilic synthetic polymer block segment, are capable of driving mechano-responsive supramolecular sol-to-gel-to-sol and sol-to-gel-to-gel transitions reversibly, which allow also for injection-based processing and self-healing behaviors. A new type of polypeptide-based organogelator, methoxy poly(ethylene glycol)-block-poly(γ-benzyl-l-glutamate-co-glycine) (mPEG-b-P(BLG-co-Gly)), is facilely synthesized by statistical ring-opening copolymerizations (ROPs) of γ-benzyl-l-glutamate (BLG) and glycine (Gly) NCAs initiated by mPEG-amine. These systems exhibit tunable secondary structures and result in sonication stimulus responsiveness of the organogels with the polypeptide segment variation, controlled by varying the ratio of BLG NCA to Gly NCA during the copolymerizations. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) studies indicate the α-helical component decreases while the β-sheet content increases systematically with a higher mole fraction of Gly in the polypeptide segment. The supramolecular assembly of β-sheet nanofibrils, having a tunable width over the range of 10.4 – 14.5 nm with varied BLG to Gly ratio, are characterized by transmission electron microscopy (TEM). The further self-assembly of these nanostructures into 3-D gel networks within N,N-dimethylformamide (DMF) occurs at low critical gelation concentrations (CGC) (lowest ca. 0.6 wt %). Increased BLG to Gly ratios lead to an increase of the α-helical component in the secondary structures of the polypeptide segments, resulting in wider and more flexible nanofibrils. The presence of α-helical component in the polymers enhances the stability of the organogels against sonication, and instantaneous gel-to-gel transitions are observed as in situ reconstruction of networks occurs within the gelled materials after sonication. In marked contrast, the β-sheet-rich gel, prepared from mPEG-b-PGly, exhibits an instant gel-to-sol transition after sonication is applied. The CGC concentration and stiffness of this mPEG-b-P(BLG-co-Gly) organogel system can be tuned by simply varying the percentages of α-helix and β-sheet in the secondary structures through control of the BLG to Gly ratio during synthesis. The mechanical properties of these organogels are studied by dynamic mechanical analyses (DMA), having storage moduli of ca. 12.1 kPa at room temperature. The injectability and self-healing capabilities are demonstrated by direct observation of the macroscopic self-healing behavior experiment.

Multi-responsive hydrogels derived from the self-assembly of tethered allyl-functionalized racemic oligopeptides

“…4.67 Å was described in a variety of β -sheet forming peptides as a characteristic hydrogen bonding length in the conformation of β- sheet secondary structures. 37, 54, 55 This WAXS signal overlapped with the 120 reflection of monoclinic PEG crystals, 49 which together with the signal corresponding to a d spacing of 3.86 Å correlated well with the crystallization and melting peaks in the DSC trace (Fig. S3).…”

“…Recently, gels composed of PEG- b - β -sheet-peptides synthesized by ring-opening polymerization (ROP) of N -carboxyanhydrides (NCAs) have been described by Jeong, 33 Heise, 34 Li, 35 and Chen 36 to show a reverse thermal gelation profile (heat-induced sol-to-gel transition), and have been reported by our group to exhibit gel-tosol or gel-to-gel behavior with sonication. 37 To the best of our knowledge, oligo or polyDLAG have not been used directly in the formation of hydrogels. Therefore, we chose to investigate this system to determine its stimuli-responsive properties by seeking a suitable chemical structure and hydrophobichydrophilic balance.…”

Polypeptide-participating complex nanoparticles with improved salt-tolerance as excellent candidates for intelligent insulin delivery

“…Synthetic polypeptides have drawn increasing attention as building blocks for construction of nanomaterials, 43 and been widely studied for various biomedical applications including drug delivery, biosensors and diagnostics, [44][45][46][47][48][49] due to their excellent biocompatibility and biodegradability. For example, copolymers containing a polypeptide backbone and PBA as pendant groups have been prepared to study glucose-dependent insulin release behavior at physiological pH.…”

A vegetable oil-based organogel for use in pH-mediated drug delivery

“…The G´ value of the organogel was observed to be 8.3 x 10 3 Pa, which compares well with other organogels reported in the literature. 41 T increase in frequency and remained below 1, indicating that the gel became more elastic and dissipated less energy (Fig. 3c).…”