title: Studies of chain substitution caused sub-fibril level differences in stiffness and ultrastructure of wildtype and oim/oim collagen fibers using multifrequency-AFM and molecular modeling.
abstract: Molecular alteration in type I collagen, i.e., substituting the α2 chain with α1 chain in tropocollagen molecule, can cause osteogenesis imperfecta (OI), a brittle bone disease, which can be represented by a mouse model (oim/oim). In this work, we use dual-frequency Atomic Force Microscopy (AFM) and incorporated with molecular modeling to quantify the ultrastructure and stiffness of the individual native collagen fibers from wildtype (+/+) and oim/oim diseased mice humeri. Our work presents direct experimental evidences that the +/+ fibers have highly organized and compact ultrastructure and corresponding ordered stiffness distribution. In contrast, oim/oim fibers have ordered but loosely packed ultrastructure with uncorrelated stiffness distribution, as well as local defects. The molecular model also demonstrates the structural and molecular packing differences between +/+ and oim/oim collagens. The molecular mutation significantly altered sub-fibril structure and mechanical property of collagen fibers. This study can give the new insight for the mechanisms and treatment of the brittle bone disease.
authors: Department of Mechanical Engineering, National University of Singapore, Singapore.
authors: Tao
authors: T
authors: Li
authors: Department of Civil Engineering, National Taiwan University, Taipei 10617, Taiwan; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Shu-Wei
authors: SW
authors: Chang
authors: Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
authors: Naiara
authors: N
authors: Rodriguez-Florez
authors: Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: Markus J
authors: MJ
authors: Buehler
authors: Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA. Electronic address: s.shefelbine@neu.edu.
authors: Sandra
authors: S
authors: Shefelbine
authors: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: mingdao@mit.edu.
authors: Ming
authors: M
authors: Dao
authors: Department of Mechanical Engineering, National University of Singapore, Singapore. Electronic address: mpezk@nus.edu.sg.
authors: Kaiyang
authors: K
authors: Zeng
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry; D024042:Collagen Type I / Q000737:chemistry* / Q000648:ultrastructure*; D055119:Elastic Modulus; D018625:Microscopy, Atomic Force / Q000379:methods*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D000072417:Protein Domains; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D024042:Collagen Type I
keywords: Bone; Collagen; Dual-frequency AFM; Oim; Stiffness