Location: Functional Foods ResearchTitle: Multi-hierarchical self-assembly of a collagen mimetic peptide from triple helix to nanofibre and hydrogel) Author
|O'leary, Lesley e.r.|
Submitted to: Nature
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/25/2011
Publication Date: 8/1/2011
Citation: O'Leary, L.E.R., Fallas, J.A., Bakota, E.L., Kang, M.K., Hartgerink, J.D. 2011. Multi-hierarchical self-assembly of a collagen mimetic peptide from triple helix to nanofibre and hydrogel. Nature. DOI: 10.1038/NCHEM.1123. Interpretive Summary: In this research, we re-created the structure of a collagen gel using a synthetic peptide. Collagen is the most abundant protein in the body and is responsible for providing structure to tissues. As a result, collagen is highly attractive for use in biomedical applications such as cell scaffolds and regenerative medicine. However, collagen must currently be purified from natural sources. The creation of synthetic collagen has challenged researchers for decades. The folded collagen protein adopts a characteristic triple-helical structure, which assembles with other triple helices to form fibers. The design and synthesis of a protein that will fold into triple helices has been one of the major obstacles in the creation of synthetic collagen. In this research, we have demonstrated that a rationally designed synthetic peptide can fold into triple helices, which self-assemble to form a collagen-like gel. This gel is similar to natural collagen gels in many respects: it has a fibrous structure as observed by electron microscopy, and it is degraded by collagenase enzymes in a similar fashion to native collagen. Because of collagen’s importance to tissue structure, we expect this peptide (and those based on its design) will play a major role in products related to cell scaffolds, regenerative medicine, and drug delivery.
Technical Abstract: Replicating the multi-hierarchical self-assembly of collagen has long-attracted scientists, from both the perspective of the fundamental science of supramolecular chemistry and that of potential biomedical applications in tissue engineering. Many approaches to drive the self-assembly of synthetic systems through the same steps as those of natural collagen (peptide chain to triple helix to nano'bres and, 'nally, to a hydrogel) are partially successful, but none simultaneously demonstrate all the levels of structural assembly. Here we describe a peptide that replicates the self-assembly of collagen through each of these steps. The peptide features collagen’s characteristic proline-hydroxyproline-glycine repeating unit, complemented by designed salt-bridged hydrogen bonds between lysine and aspartate to stabilize the triple helix in a sticky-ended assembly. This assembly is propagated into nano'bres with characteristic triple helical packing and lengths with a lower bound of several hundred nanometres. These nano'bres form a hydrogel that is degraded by collagenase at a similar rate to that of natural collagen.