Multi-hierarchical self-assembly of a collagen mimetic peptide from triple helix to nanofibre and hydrogel

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 nanofibres and, finally, 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 nanofibres with characteristic triple helical packing and lengths with a lower bound of several hundred nanometres. These nanofibres form a hydrogel that is degraded by collagenase at a similar rate to that of natural collagen.

Electrostatics in Protein Engineering and Design

“…The same scoring function was recently extended to design of collagen heterotrimers where three www.intechopen.com peptides A, B and C combine specifically to form an ABC heterotrimer (Xu et al 2011). Molecules such as these are now finding applications as synthetic biomaterials where the electrostatic control of self-assembly is responsible for directing the formation of protein fibers (Pandya et al 2000;O'Leary et al 2011). …”

Rational design of fiber forming supramolecular structures

“…Here, short-chain polypeptides, consisting of approximately 24-36 amino acids, self-assemble into triple helices and can further mimic all stages of natural collagen's multi-hierarchical self-assembly. 6,119 Most commonly, proline and 4-hydroxyproline occupy the Xxx and Yyy positions of natural collagen, while recent studies have begun to investigate self-assembling CMPs with a variety of amino acid mutations. 34 This repeating triplet plays a role in stabilizing triple helix formation.…”

“…[1][2][3][4][5] Through advances in nanotechnology and peptide chemistry it is now possible to recreate the fundamental building blocks of mammalian life-such as collagen and elastin in their native hierarchical structures. [6][7][8] Peptide-based materials stand at the forefront of several tissue engineering strategies. [9][10][11][12][13][14][15][16][17][18] Owing to the modular nature peptide-based materials, a variety of different moieties can be introduced.…”

Effect of noncovalent interaction on the self-assembly of a designed peptide and its potential use as a carrier for controlled bFGF release

“…1 Inspired by nature, a variety of biomolecules, including amino acids, [2][3][4] peptides, [5][6][7][8] proteins, 9,10 DNA, 11 saccharides, 12 lipids, 13,14 and their derivatives, [15][16][17] have been used as versatile building blocks for the design of functional structures at the nanoscale and microscale through molecular self-assembly. Building blocks have unique physical and chemical properties, which, if harnessed effectively, can result in materials with highly functional characteristics.…”

“…liu et al monomer consisting of a structural motif that folds to adopt a known secondary structure such as the α-helix, 15,27 β-strand, 8,23 and β-hairpin. 7,19 Noncovalent interactions, including hydrophobic, hydrophilic, π-stacking, hydrogen bonding, and polypeptide chain entropy (∆S C ), play important roles in triggering the assembly of peptide nanostructures.…”