Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nano Lett. 2011 Feb 9;11(2):757-66. doi: 10.1021/nl103943u. Epub 2011 Jan 5.
Collagen constitutes one-third of the human proteome, providing mechanical stability, elasticity, and strength to organisms and is the prime construction material in biology. Collagen is also the dominating material in the extracellular matrix and its stiffness controls cell differentiation, growth, and pathology. However, the origin of the unique mechanical properties of collagenous tissues, and in particular its stiffness, extensibility, and nonlinear mechanical response at large deformation, remains unknown. By using X-ray diffraction data of a collagen fibril (Orgel, J. P. R. O. et al. Proc. Natl. Acad. Sci. 2006, 103, 9001) here we present an experimentally validated model of the nanomechanics of a collagen microfibril that incorporates the full biochemical details of the amino acid sequence of constituting molecules and the nanoscale molecular arrangement. We demonstrate by direct mechanical testing that hydrated (wet) collagen microfibrils feature a Young's modulus of ≈300 MPa at small, and ≈1.2 GPa at larger deformation in excess of 10% strain, which is in excellent agreement with experimental data. We find that dehydrated (dry) collagen microfibrils show a significantly increased Young's modulus of ≈1.8-2.25 GPa, which is in agreement with experimental measurements and owing to tighter molecular packing. Our results show that the unique mechanical properties of collagen microfibrils arise due to their hierarchical structure at the nanoscale, where key deformation mechanisms are straightening of twisted triple-helical molecules at small strains, followed by axial stretching and eventual molecular uncoiling. The establishment of a model of hierarchical deformation mechanisms explains the striking difference of the elastic modulus of collagen fibrils compared with single molecules, which is found in the range of 4.8 ± 2 GPa, or ≈10-20 times greater. We find that collagen molecules alone are not capable of providing the broad range of mechanical functionality required for physiological function of collagenous tissues. Rather, the existence of an array of deformation mechanisms, derived from the hierarchical makeup of the material, is critical to the material's ability to confer key mechanical properties, specifically large extensibility, strain hardening, and toughness, despite the limitation that collagenous materials are constructed from only few distinct amino acids. The atomistic model of collagen microfibril mechanics now enables the bottom-up elucidation of structure-property relationships in a broader class of collagen materials (e.g., tendon, bone, cornea), including studies of genetic disease where the incorporation of biochemical details is essential. The availability of a molecular-based model of collagen tissues may eventually result in novel nanomedicine approaches to develop treatments for a broad class of collagen diseases and the design of de novo biomaterials for regenerative medicine.
胶原蛋白构成了人类蛋白质组的三分之一，为生物体提供机械稳定性、弹性和强度，是生物学中主要的结构材料。胶原蛋白也是细胞外基质的主要成分，其硬度控制着细胞的分化、生长和病理。然而，胶原蛋白组织独特的力学性质的起源，特别是其硬度、可拉伸性和大变形下的非线性力学响应，仍然未知。本文利用胶原蛋白原纤维的 X 射线衍射数据（Orgel, J. P. R. O. 等人。Proc. Natl. Acad. Sci. 2006, 103, 9001），提出了一个实验验证的胶原微纤维纳米力学模型，该模型结合了构成分子的完整生化细节和纳米尺度的分子排列。通过直接力学测试，我们证明了水合（湿）胶原微纤维在小变形时具有约 300 MPa 的杨氏模量，在超过 10%应变的大变形时具有约 1.2 GPa 的杨氏模量，这与实验数据非常吻合。我们发现，脱水（干）胶原微纤维的杨氏模量显著增加，约为 1.8-2.25 GPa，这与实验测量结果一致，这是由于分子排列更紧密。我们的结果表明，胶原微纤维独特的力学性质源于其纳米尺度的层次结构，关键的变形机制是在小应变下扭曲的三螺旋分子的伸直，然后是轴向拉伸和最终的分子解旋。分层变形机制模型的建立解释了胶原纤维弹性模量与单分子显著差异的原因，实验发现其范围在 4.8±2 GPa，或约 10-20 倍。我们发现，胶原分子本身并不能提供胶原组织生理功能所需的广泛的机械功能。相反，源于材料层次结构的一系列变形机制的存在，对于材料赋予关键力学性能至关重要，特别是大的可拉伸性、应变硬化和韧性，尽管胶原材料仅由少数几种不同的氨基酸构建。胶原微纤维力学的原子模型现在可以从底层阐明更广泛的胶原材料（例如肌腱、骨骼、角膜）的结构-性能关系，包括在遗传疾病中，结合生化细节是必不可少的。胶原组织的分子模型的出现可能最终导致开发治疗广泛的胶原疾病的新型纳米医学方法和设计用于再生医学的新型生物材料。
