Secondary-Structure-Mediated Hierarchy and Mechanics in Polyurea–Peptide Hybrids

Abstract

Peptide-polymer hybrids combine the hierarchy of biological species with synthetic concepts to achieve control over molecular design and material properties. By further incorporating covalent cross-links, the enhancement of molecular complexity is achieved, allowing for both a physical and covalent network. In this work, the structure and function of poly(ethylene glycol) (PEG)-network hybrids are tuned by varying peptide block length and overall peptide content. Here the impact of poly(ε-carbobenzyloxy-l-lysine) (PZLY) units on block interactions and mechanics is explored by probing secondary structure, PEG crystallinity, and hierarchical organization. The incorporation of PZLY reveals a mixture of α-helices and β-sheets at smaller repeat lengths ( n = 5) and selective α-helix formation at a higher peptide molecular weight ( n = 20). Secondary structure variations tailored the solid-state film hierarchy, whereby nanoscale fibers and microscale spherulites varied in size depending on the amount of α-helices and β-sheets. This long-range ordering influenced mechanical properties, resulting in a decrease in elongation-at-break (from 400 to 20%) with increasing spherulite diameter. Furthermore, the reduction in soft segment crystallinity with the addition of PZLY resulted in a decrease in moduli. It was determined that, by controlling PZLY content, a balance of physical associations and self-assembly is obtained, leading to tunable PEG crystallinity, spherulite formation, and mechanics.

Peptide–polyurea hybrids: a platform for tunable, thermally-stable, and injectable hydrogels

“…45 In the case of the PZLY-PEG PPU hybrids, it is likely that the similarity of the a-helical pitch from both the PZLY segments and 7 2 PEG promote cooperative hierarchical assembly, which has been identified as the mechanism to induce ribbon-like assemblies in PEG-PBLA block copolymers. 21 However, the fibrillar architectures observed in these PPU hydrogels are significantly longer and more ordered, which may be attributed to a combination of secondary structure hydrogen bonding of the peptide segment and the amphiphilic character of the PZLY and PEG blocks, resulting in packing of the nanofibers to form the hydrogel. 42 The assembly of PPUs into long fiber bundles exhibits similarity to structures arising from the self-assembly of small peptide amphiphiles, where the mechanism of assembly relies first on the association of small peptide aggregates, followed by nanofiber growth and twisting into physically crosslinked hydrogels.…”

“…This work draws on previous synthetic strategies to formulate PPUs with tunable secondary structure composition, mechanical properties, and morphology in the solid state. 21,25 To facilitate macromolecular design that dictates self-assembly, flow properties, and structure of hydrated hybrids, a series of PPUs were synthesized. NCA ring opening polymerization initiated by PEG diamine was used to form the triblock precursors (step 1, Fig.…”

“…Based on previous research, the PZLY segment length is expected to modulate the relative amount of a-helix/b-sheet structures present in the polyurea hybrids. 21,25 The peptide content was maintained at 10 wt% in all PPU samples to directly target the impact of peptide secondary structure and chain length, as variations in peptide content also can influence PPU properties. 20 Additionally, a control polyurea (PEG-PU) was prepared without peptide in the soft segment to examine the impact of PZLY and PBLA segments on gelation behavior.…”

“…An additional class of nature-inspired materials, peptide-polyurea (PPU) hybrids, harness interactions between peptides and synthetic polymer blocks resulting in tunable mechanics and stimuli responsiveness in the solid state. [20][21][22] This PPU platform offers an opportunity to develop dynamic hydrated networks, as it is facile to achieve higher molecular weights while also incorporating peptide functionalities that result in solid-state, tunable hierarchical assembly. However, these systems are not typically utilized as hydrated biomaterials with only limited understanding of the structural factors that influence hydrogel mechanics and morphology.…”