Structure-mechanics relationships of collagen fibrils in the Osteogenesis Imperfecta Mouse model
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Author(s)
Type
Journal Article
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. Since
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 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 animals, we found 33% lower
indentation 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 to 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 osteogenesis imperfecta. 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.
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. Since
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 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 animals, we found 33% lower
indentation 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 to 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 osteogenesis imperfecta. 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.
Date Issued
2015-10-14
Date Acceptance
2015-09-09
Citation
Journal of the Royal Society Interface, 2015, 12
ISSN
1742-5689
Publisher
Royal Society, The
Journal / Book Title
Journal of the Royal Society Interface
Volume
12
Copyright Statement
© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution
License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original
author and source are credited.
License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original
author and source are credited.
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Publication Status
Published
Article Number
20150701