title: Structure-mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model.
abstract: The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry.
authors.affiliation: Institute for Lightweight Design and Structural Biomechanics, Vienna University of Technology, Getreidemarkt 9, Vienna 1060, Austria Bioengineering Research Group, Faculty of Engineering and the Environment, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: O G
authors.initials: OG
authors.lastname: Andriotis
authors.affiliation: Department of Civil Engineering, National Taiwan University, Taipei 10617, Taiwan, Republic of China Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Chang
authors.affiliation: Department of Bioengineering, Imperial College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Vanleene
authors.affiliation: The Brooke Laboratories, Division of Infection, Inflammation and Immunity, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: P H
authors.initials: PH
authors.lastname: Howarth
authors.affiliation: The Brooke Laboratories, Division of Infection, Inflammation and Immunity, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: D E
authors.initials: DE
authors.lastname: Davies
authors.affiliation: Department of Bioengineering, Imperial College London, London, UK Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Shefelbine
authors.affiliation: Center for Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA Center for Computational Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Buehler
authors.affiliation: Institute for Lightweight Design and Structural Biomechanics, Vienna University of Technology, Getreidemarkt 9, Vienna 1060, Austria Bioengineering Research Group, Faculty of Engineering and the Environment, University of Southampton, Southampton SO17 1BJ, UK pthurner@ilsb.tuwien.ac.at.
authors.forename: P J
authors.initials: PJ
authors.lastname: Thurner
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics* / Q000502:physiology; D003198:Computer Simulation; D003432:Cross-Linking Reagents; D004195:Disease Models, Animal; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018625:Microscopy, Atomic Force; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D011487:Protein Conformation; D013314:Stress, Mechanical
chemical_list: D024042:Collagen Type I; D003432:Cross-Linking Reagents
keywords: atomic force microscopy; atomistic simulations; collagen; mechanics; osteogenesis imperfecta; structure