Morphological transformations in a dually thermoresponsive coil–rod–coil bioconjugate

Abstract

We report the conformational and assembly behavior of a thermoresponsive triblock biohybrid conjugate under aqueous conditions. The triblock comprises of poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA) conjugated to the ends of a triple-helix forming collagen-like peptide. The circular dichroism (CD) experiment confirms the ability of the collagen-like peptide middle block to assemble as a triple helix in the hybrid conjugate. Above the LCST (~35 °C), the collapse of the thermoresponsive PDEGMEMA polymer at the ends of the peptide domain resulted in a concomitant increase in the conformational stability of the peptide domain towards thermal denaturation. Upon cooling back, the kinetic conformational refolding behavior was still observed for the peptide domain in the hybrid conjugate. Static light scattering (SLS) experiments suggested the formation of supramolecular structures upon increasing solution temperatures to above the LCST. The scattering intensity increased with increasing temperature, until at 75 °C then it was found to decrease. Cryogenic scanning electron microscopy and regular transmission electron microscopy suggested the formation of spherical aggregates that increased in size with increasing temperature up to 65 °C and a morphological transformation into fibrils was also observed at 75 °C. The synergistic effect of dual thermoresponsive behavior from the peptide and the polymer block in the triblock hybrid is suggested for the observed conformational and assembly behaviors.

Noncovalent Modulation of the Inverse Temperature Transition and Self-Assembly of Elastin-b-Collagen-like Peptide Bioconjugates

“…Presumably, the collapse of the ELP domain at the elevated temperatures anchors the CLP and stabilizes it against unfolding, similar to our previously reported results for a polymer-conjugated CLP. 15b,19 The refolding of the CLP triple helix (Figure 1c,d) is likewise accelerated by the ELP anchoring of the CLP, owing to the increase in the local concentration of the CLP strands. 15,19,20 While a rate constant of 1.14 × 10 7 M −2 ·s −1 was observed for the refolding reaction of the CLP, the diblock shows a higher rate constant of 4.63 × 10 7 M −2 ·s −1 .…”

“…Despite this widespread use, the utilization of CLPs as domains in responsive nanoparticles has been described in only a very limited number of reports. 15 …”

Hybrid Block Copolymers Constituted by Peptides and Synthetic Polymers: An Overview of Synthetic Approaches, Supramolecular Behavior and Potential Applications

“…The main relevant result was that the α-helix secondary structure was empowered on increasing the length of the PEG chain. Thus, the incorporation of such side chains had a significant stabilizing effect on the helical structure Kiick et al [84] have recently proposed the study of the morphological transformation in a dually thermoresponsive coil-rod-coil bioconjugated based on poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA) linked to both ends of a triple-helix forming collagen-like peptide. The ability of the middle block to assemble as a triple helix in the hybrid conjugate was confirmed by circular dichroism since a local positive maximum around 227 nm was clearly detected.…”

Self‐assembly and responsiveness of polypeptide‐based block copolymers: How “Smart” behavior and topological complexity yield unique assembly in aqueous media

“…Kiick and coworkers recently reported the synthesis of BAB systems containing a collagen mimicking sequenced peptide. 93 Here, they utilized the telechelic amine peptide in a coupling strategy with activated ester terminated poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA.) Similar strategies could be used to create this topology with a hydrophilic homopeptide, synthesized through ROP of NCAs, employing a small molecule diamine initiator as the center block and either a hydrophobic synthetic polymer/polypeptide as the outer blocks.…”

“…Similar to these gold nanorod systems, Kiick and coworkers recently reported the aqueous assembly of fully organic coilrod-coil BAB copolymers. 93 Their model copolymer for this study was poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA) attached to the outside of a triple-helix forming collagen-like peptide, PDEGMEMA(coil)-collagen-peptide(rod)-PDEGMEMA(coil). As in the case of gold nanorod systems, these molecules were found to form 3D toroid-type spherical assemblies through the bending constraint that the triple-helix forming peptide imposes.…”