To achieve self‐assembled collagen mimetic fibrils using designed peptides

Abstract It has proven challenging to obtain collagen‐mimetic fibrils by protein design. We recently reported the self‐assembly of a mini‐fibril showing a 35 nm, D ‐period like, axially repeating structure using the designed triple helix Col108. Peptide Col108 was made by bacterial expression using a synthetic gene; its triple helix domain consists of three pseudo‐identical units of amino acid sequence arranged in tandem. It was postulated that the 35 nm d ‐period of Col108 mini‐fibrils originates from the periodicity of the Col108 primary structure. A mutual staggering of one sequence unit of the associating Col108 triple helices can maximize the inter‐helical interactions and produce the observed 35 nm d ‐period. Based on this unit‐staggered model, a triple helix consisting of only two sequence units is expected to have the potential to form the same d ‐periodic mini‐fibrils. Indeed, when such a peptide, peptide 2U108, was made it was found to self‐assemble into mini‐fibrils having the same d ‐period of 35 nm. In contrast, no d ‐periodic mini‐fibrils were observed for peptide 1U108, which does not have long‐range repeating sequences in its primary structure. The findings of the periodic mini‐fibrils of Col108 and 2U108 suggest a way forward to create collagen‐mimetic fibrils for biomedical and industrial applications.