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: O G Andriotis, S W Chang, M Vanleene, P H Howarth, D E Davies, S J Shefelbine, M J Buehler, P J Thurner
• Journal: Journal of the Royal Society, Interface (J R Soc Interface) Vol. 12 Issue 111 Pg. 20150701 (Oct 06 2015) ISSN: 1742-5662 [Electronic] England
• PMID: 26468064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015 The Authors.

Chemical References

• Collagen Type I
• Cross-Linking Reagents

Topics

• Animals
• Collagen Type I (genetics, physiology)
• Computer Simulation
• Cross-Linking Reagents
• Disease Models, Animal
• Gene Deletion
• Male
• Mice
• Mice, Transgenic
• Microscopy, Atomic Force
• Mutation
• Osteogenesis Imperfecta (genetics, metabolism)
• Phenotype
• Protein Conformation
• Stress, Mechanical