Collagen I is a key protein during fibrosis, where its increased deposition and crosslinking fuel disease progression. To investigate the role of related cell-matrix interactions in this misregulated wound healing process, culture models are needed that capture pivotal aspects of this collagenous extracellular matrix (ECM) for hypothesis testing, including precise control of matrix mechanical properties (Young’s modulus, E ~ 1-20 kPa), fibrillar structure, and biochemical content. Here, multifunctional collagen mimetic peptides (mfCMPs) were synthesized for the assembly of a fibrous matrix that subsequently can be covalently crosslinked to impart robust mechanical properties to mimic healthy to diseased loose connective tissues. Specifically, a mfCMP was synthesized containing i) repeats of the tripeptide subunit proline-hydroxyproline-glycine (POG)n for triple helix formation at physiological temperatures; ii) allyloxycarbonyl (alloc) group for covalent modification; and iii) pi-pi stacking groups on each terminus for the formation of long fibrils and fibers. The triple helix formation was confirmed with circular dichronism spectroscopy, where a melting temperature of 62 °C in water was observed. After self-assembly, a microscale, interconnected fibrous structure was observed using transmission electron microscopy. The fibril widths were found to be in the range of 10 to 100 nm with studied concentrations between 1 mg/mL and 10 mg/mL. Both the width and the length of the CMP fibers were much greater than triple helix (1.5 nm in width and 10 nm in length), indicating both linear and lateral assembly. A mfCMP aqueous solution (1 wt%) formed a physical hydrogel (storage modulus, G’ ~ 40 Pa) after 10 hours of room temperature incubation. The CMP fibrous network was also incorporated into a covalently crosslinked poly(ethylene glycol) (PEG)-based hydrogel using photoinitiated thiol–ene click chemistry to achieve soft-tissue-like moduli. These mfCMP hydrogels have great potential to serve as a model system to mimic collagenous tissues and fibrotic microenvironments and broadly can be used to understand and direct tissue remodeling processes.

Mimicking collagenous tissues with dynamically controlled hydrogels through peptide self-assembly and light-mediated click chemistry

251st National Meeting (2016)

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