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

Biomaterials. 2016 Nov;107:15-22. doi: 10.1016/j.biomaterials.2016.08.038. Epub 2016 Aug 24.


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.

Keywords: Bone; Collagen; Dual-frequency AFM; Oim; Stiffness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Amino Acids / chemistry
  • Collagen Type I / chemistry*
  • Collagen Type I / ultrastructure*
  • Elastic Modulus
  • Microscopy, Atomic Force / methods*
  • Models, Molecular*
  • Molecular Dynamics Simulation*
  • Protein Conformation
  • Protein Domains
  • Stress, Mechanical
  • Structure-Activity Relationship


  • Amino Acids
  • Collagen Type I