title: Mechanical recruitment of N- and C-crosslinks in collagen type I.
abstract: Collagen type I is an extracellular matrix protein found in connective tissues such as tendon, ligament, bone, skin, and the cornea of the eyes, where it functions to provide tensile strength; it also serves as a scaffold for cells and other extracellular matrix components. A single collagen type I molecule is composed of three amino acid chains that form a triple helix for most of the molecule's length; non-triple-helical extensions called N- and C-telopeptides are located at the amino/N-terminal and carboxy/C-terminal ends of the molecule, respectively. In two of the three chains, the C-telopeptide has been reported to possess a hair-pin/hook conformation, while the three N-telopeptides display a more extended structure. These telopeptides are crucial for the formation of enzymatic covalent crosslinks that form in collagens near their N- and C-ends. Such crosslinks provide structural integrity, strength, and stiffness to collagenous tissues. However, deformation mechanisms of N- and C-crosslinks and functional roles for the N- and C-telopeptide conformations are not yet well known. By performing molecular dynamics simulations, we demonstrated that two dehydro-hydroxylysino-norleucine crosslinks, positioned at the N- and C-crosslinking sites, exhibited a two-stage response to the mechanical deformation of their parent molecules. We observed that the N-crosslink served as the first responder to mechanical deformation, followed by the C-crosslink. The results of our simulations suggest a mechanical recruitment mechanism for N- and C-crosslinks. Understanding this mechanism will be crucial for the development of larger-scale predictive models of the mechanical behavior of native collagenous tissues, engineered tissues, and collagen-based materials.
authors.affiliation: Virginia Polytechnic Institute and State University, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Musculoskeletal Tissue Regeneration Laboratory, 330 Kelly Hall, 325 Stanger St., Blacksburg, VA 24061, USA; Virginia Polytechnic Institute and State University, Department of Engineering Science and Mechanics, Mechanics of Soft Biological Systems Laboratory, 202 Norris Hall, 495 Old Turner St., Blacksburg, VA 24061, USA.
authors.forename: Albert L
authors.initials: AL
authors.lastname: Kwansa
authors.affiliation: Virginia Polytechnic Institute and State University, Department of Engineering Science and Mechanics, Mechanics of Soft Biological Systems Laboratory, 202 Norris Hall, 495 Old Turner St., Blacksburg, VA 24061, USA.
authors.forename: Raffaella
authors.initials: R
authors.lastname: De Vita
authors.affiliation: Virginia Polytechnic Institute and State University, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Musculoskeletal Tissue Regeneration Laboratory, 330 Kelly Hall, 325 Stanger St., Blacksburg, VA 24061, USA; Rutgers University, Department of Biomedical Engineering, Musculoskeletal Tissue Regeneration Laboratory, 317 BME Building, 599 Taylor Rd., Piscataway, NJ 08854, USA. Electronic address: joseph.freeman@rutgers.edu.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Freeman
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D024042:Collagen Type I / Q000737:chemistry* / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D000596:Amino Acids; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide
keywords: Collagen type I; Crosslink; Molecular dynamics; Molecular model; Telopeptide