Structure-mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model.

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.

Relationships between density and Young's modulus with microporosity and physico-chemical properties of Wistar rat cortical bone from growth to senescence.

The aim of this study is to assess density and elastic properties of Wistar rat cortical bone from growth to senescence and to correlate them with morphological and physico-chemical properties of bone. During growth (from 1 to 9 months), bone density and Young's modulus were found to increase from 1659+/-85 to 2083+/-13 kg m(-3) and from 8+/-0.8 to 19.6+/-0.7 GPa respectively. Bone microporosity was found to decrease from 8.1+/-0.7% to 3.3+/-0.7%. Physico-chemical investigations exhibited a mineralization of bone matrix and a maturation of apatite crystals, as protein content decreased from 21.4+/-0.2% to 17.6+/-0.6% and apatite crystal size and carbonate content increased (c-axis length: from 151 to 173 A and CO(3)W%: from 4.1+/-0.3% to 6.1+/-0.2%). At adult age, all properties stabilized. During senescence, a slow decrease of mechanical properties was first observed (from 12 to 18 months, rho=2089+/-14 to 2042+/-30 kg m(-3) and E(3)=19.8 +/-1.3 to 14.8+/-1.5 GPa), followed by a stabilization. Physico-chemical properties stabilized while microporosity increased slightly (from 3.3% to 4%) but not significantly (p>0.05). A multiple regression analysis showed that morphological and physico-chemical properties had significant effects on density regression model. Microporosity had a greater effect on Young's modulus regression model than physico-chemical properties. This study showed that bone structure, mineralization and apatite maturation should be considered to improve the understanding of bone mechanical behaviour.