Structure-mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model.
Structure-mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model.
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DOI：
10.1098/rsif.2015.0701
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发表时间：
2015-10-06
期刊：
影响因子：
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通讯作者：
Thurner PJ
中科院分区：
文献类型：
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作者：
Andriotis OG;Chang SW;Vanleene M;Howarth PH;Davies DE;Shefelbine SJ;Buehler MJ;Thurner PJ
胶原蛋白分子是由两条α1(I)链和一条α2(I)链组成的三螺旋结构，是胶原原纤维的组成部分。然而，在严重的成骨不全（OIM）小鼠模型中，COL1A2基因的缺失导致α2(I)链被一条α1(I)链取代。由于这种替代在组织和器官水平上严重损害了富含胶原的组织的结构和力学，因此本研究的主要目的是研究OIM胶原原纤维的结构和力学是如何改变的。比较原子力显微镜成像结果和OIM和野生型（WT）动物胶原原纤维的悬臂纳米压痕结果，我们发现，当风干（存在结合水）时，OIM的压痕模量降低了33%，而在磷酸盐缓冲盐水溶液（PBS）中完全水化（存在结合水和非结合水）时，OIM胶原原纤维的压痕模量几乎是WT胶原原纤维的5倍。这些机械变化伴随着PBS水化后肿胀受损。我们的实验和原子模拟结果显示了OIM中胶原基因突变如何在单个胶原纤维水平上改变结构和力学。我们设想实验和建模方法的结合可以在胶原纤维水平上对胶原结构或化学的几乎任何改变进行机械表型分析。
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.