Structure and Mechanical properties of Collagen fibrils

胶原原纤维的结构和机械性能

• 批准号: RGPIN-2018-03781
• 负责人: Kreplak, Laurent
• 金额: $ 2.48万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=685378
• 关键词: Structure; Mechanical; properties; Collagen; fibrils

Collagen is the protein building block of most mammalian tissues such as tendon, arteries, skin and bone. It is often sourced from various animal tissues and used in a wide array of medical and cosmetic applications such as skin fillers, wound dressing, and guided tissue regeneration. In its crudest extracted form, collagen is the main component of gelatin: a hydrogel used mostly as a food ingredient and as a nonmedicinal ingredient in drugs and nutritional complements. ***Within our body, collagen forms fibrils, long cables with a diameter in the range of one thousandth of a human hair. Collagen fibrils give our tendons tensile properties comparable to the strongest man-made polymer materials. The assembly of collagen fibrils is a spontaneous process that cells tightly control to achieve a specific structural-mechanical relationship for each tissue. For example, tendons are typically split into two broad classes, the positional ones that are responsible for precise bone positioning such as in the hand, and the energy-storing ones like the Achilles at the heel of the foot that store elastic energy during movement. It is already established that these two types of tendons have different tensile properties. We recently demonstrated, using an atomic force microscopy based approach, that the same dichotomy is true at the collagen fibril level. ***This unexpected finding offers the opportunity to contrast the structural-mechanical relationships of the two types of fibrils. This is a challenging task that requires sensitive structural probes at the single fibril level compatible with tensile testing techniques at the same scale. To this end, I have assembled a strong team of students and collaborators, and identified three promising techniques: atomic force microscopy for single fibril imaging, spectroscopy and manipulation; nanoscale X-ray diffraction for probing molecular packing at high spatial resolution; and second harmonic generation microscopy for time-resolved studies. We will combine these cutting-edge approaches with theoretical models inspired from soft-matter physics concepts to provide a complete picture of how the structure of collagen fibrils extracted from the two different types of tendon, positional versus energy-storing, changes during stretch and ultimately fails.***Our findings will have applications in the biomedical field where novel treatments of tendon injuries, as well as other soft-tissue trauma, could benefit from understanding the molecular nature and determinants of mechanical damage in collagen fibrils. To that end, I already have contacts with the Nova Scotia Tissue Bank to ensure timely translation of the research to clinicians. Another potential area of application is in the design and production of biodegradable, high performance textiles based on proteins. **************************

胶原蛋白是大多数哺乳动物组织如肌腱、动脉、皮肤和骨骼的蛋白质构建块。它通常来源于各种动物组织，并用于广泛的医疗和美容应用，如皮肤填充物，伤口敷料和引导组织再生。在其最粗糙的提取形式中，胶原蛋白是明胶的主要成分：一种水凝胶，主要用作食品成分和药物和营养补充剂中的非药用成分。* 在我们的身体内，胶原蛋白形成原纤维，直径在人类头发千分之一范围内的长电缆。胶原纤维赋予我们的肌腱拉伸性能，可与最强的人造聚合物材料相媲美。胶原纤维的组装是一个自发的过程，细胞严格控制以实现每个组织的特定结构-机械关系。例如，肌腱通常分为两大类，负责精确骨骼定位的位置肌腱（如手部），以及在运动期间存储弹性能量的能量存储肌腱（如脚跟处的跟腱）。已经确定这两种类型的钢筋束具有不同的拉伸性能。我们最近证明，使用原子力显微镜为基础的方法，同样的二分法是真实的胶原纤维水平。* 这一出乎意料的发现提供了对比两种类型原纤维的结构-机械关系的机会。这是一项具有挑战性的任务，需要在同一尺度下与拉伸测试技术兼容的单原纤维水平的敏感结构探针。为此，我组建了一支由学生和合作者组成的强大团队，并确定了三种有前途的技术：用于单原纤维成像，光谱学和操作的原子力显微镜;用于探测高空间分辨率分子堆积的纳米级X射线衍射;以及用于时间分辨研究的二次谐波发生显微镜。我们将联合收割机结合这些尖端的方法与理论模型的灵感来自软物质物理概念，以提供一个完整的图片如何胶原纤维的结构提取的两种不同类型的肌腱，位置与能量存储，在拉伸过程中的变化，并最终失败。我们的研究结果将在生物医学领域的新的治疗肌腱损伤，以及其他软组织创伤，可以受益于了解胶原纤维的分子性质和机械损伤的决定因素的应用。为此，我已经与新斯科舍省组织库取得了联系，以确保及时将研究成果翻译给临床医生。另一个潜在的应用领域是基于蛋白质的可生物降解的高性能纺织品的设计和生产。**************************