Synthetic scaffolds for musculoskeletal tissue engineering: cellular responses to fiber parameters

Fibrous proteins of the extracellular matrix. a The basic unit of collagen fibrils is the tropocollagen triple-helix comprised of three α-chains. Each α-chain forms a helix where glycine is positioned at every third amino acid, often with glycine-proline-X or glycine-X-hydroxyproline repeats. Tropocollagen molecules form collagen fibrils by binding together in a quarter-stagger pattern that gives collagen its characteristic banding pattern. Collagen fibrils vary in diameter, alignment, and packing depending on the tissue they are found in. b Fibronectin (FN) polypeptide chains are comprised of three variable domains: FNI, FNII, and FNIII. Each polypeptide chain contains 12 FNI domains, 2 FNII domains, and 15–17 FNIII domains. Pre-mRNA splicing produces at least 20 variants of the protein in humans. Fibronectin polypeptide chains form a ‘V’ shape at the C-terminus via two disulfide bonds. Fibronectin is secreted as a globular protein that is stretched by cells into its fibrillar form. c Tenascin fibrils are comprised of varying numbers of heptad repeats, epidermal growth factor (EGF)-like repeats, fibronectin type III (FNIII) domains, and a globular fibrinogen domain capping the C-terminus. Tenascin fibrils bind at the N-terminus to form hexamers and trimers. d Tropoelastin molecules contain alternating hydrophobic domains and crosslinking domains. Elastin fibers are generally relaxed and coiled. Lysyl-oxidase crosslinks the fibers together to form a network. When the tissue is stressed, the elastin uncoils and elongates. e Each laminin contains an α-chain, a β-chain, and a γ-chain. There are five α-chain, four β-chain, and three γ-chain variants. Each chain contains a combination of laminin N-terminal domains, laminin IV type A domains, laminin IV type B domains, and EGF-like repeats. α-chains contain laminin G-like domains at the C-terminal of the peptide. Laminins form helical glycoproteins composed of three polypeptide chains (α, β, γ). There are 15 known combinations of α-, β-, and γ- chains. Three short chains (α, β, γ) at the N-terminal interact with the ECM, and a long chain (α) at the C-terminal binds to cell-membrane integrins. Laminin 111 show