Multi-Hierarchical Self-Assembly of Collagen Mimetic Peptides into AAB Type Heterotrimers, Nanofibers and Hydrogels Driven by Charged Pair Interactions

• Other Authors: Hartgerink, Jeffrey D.
• Format: Others
• Language: English
• Published: 2013
• Subjects: Applied sciences; Pure sciences; Biological sciences; Self-assembly; Collagen; Nanofibers; Hydrogels; Charged pair interactions; Triple helix; Molecular biology; Biochemistry; Nanoscience
• Online Access: http://hdl.handle.net/1911/70377

Replicating the multi-hierarchical self-assembly of collagen (peptide chain to triple helix to nanofiber and, finally, to a hydrogel) has long attracted scientists, both from the fundamental science perspective of supramolecular chemistry and for the potential biomedical applications perceived in tissue engineering. In terms of triple helical formation, collagen is the most abundant protein in the human body with at least 28 types, yet research involving collagen mimetic systems has only recently began to consider the innate ability of collagen to control helix composition and register. Collagen triple helices can be homotrimeric or heterotrimeric and while some types of natural collagen form only one specific composition of helix, others can form multiple. It is critical to fully understand and, if possible, reproduce the control that native collagen has on helix composition and register. In terms of nanofiber formation, many approaches to drive the self-assembly of synthetic systems through the same steps as natural collagen have been partially successful, but none have simultaneously demonstrated all levels of structural assembly. In this work, advancements in the ability to control helix composition and replicate the multi-hierarchical assembly of collagen are described. Both positive and negative design for the assembly of AAB type collagen heterotrimers were utilized by promoting heterotrimer formation though the use of charged amino acids to form intra-helix electrostatic interactions, while simultaneously discouraging homotrimers, resulting in the identification of multiple peptide systems with full control over the composition of the resulting triple helix. Similar salt-bridged hydrogen bonds between charged residues were incorporated into nanofiber forming peptides, one of which successfully assembled into sticky-ended triple helices, nanofibers with characteristic triple helical packing visible in the solution state, and strong hydrogels that are degraded by collagenase at a similar rate to natural collagen. Together, these results provide a better understanding of the self-assembly of collagenous sequences as well as a novel design scheme for synthetic extracellular matrix mimetics with potential applications in regenerative medicine and drug delivery.