Structure and Mechanical properties of Collagen fibrils

胶原蛋白是大多数哺乳动物组织（如肌腱、动脉、皮肤和骨骼）的蛋白质组成部分。它通常来源于各种动物组织，并广泛用于医疗和美容应用，如皮肤填充物、伤口敷料和引导组织再生。在最原始的提取形式中，胶原蛋白是明胶的主要成分：明胶是一种水凝胶，主要用作食品成分，也用作药物和营养补充剂的非药用成分。在我们体内，胶原蛋白形成原纤维，这是一种长纤维，直径约为人类头发的千分之一。胶原原纤维赋予我们的肌腱与最强的人造高分子材料相媲美的拉伸性能。胶原原纤维的组装是细胞严格控制的自发过程，以实现每个组织的特定结构-力学关系。例如，肌腱通常分为两大类，一种是负责精确定位骨骼的位置肌腱，如手部，另一种是储存能量的肌腱，如脚后跟的跟腱，在运动过程中储存弹性能量。已经确定这两种类型的肌腱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，同样的二分法是正确的，在胶原纤维水平。这一意想不到的发现为对比两种纤维的结构-力学关系提供了机会。这是一项具有挑战性的任务，需要在单纤维水平上与相同规模的拉伸测试技术兼容的敏感结构探针。为此，我组建了一个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：用于单纤维成像、光谱和操作的原子力显微镜；高空间分辨率探测分子堆积的纳米x射线衍射；二次谐波生成显微镜用于时间分辨研究。我们将把这些前沿方法与受软物质物理概念启发的理论模型结合起来，提供从两种不同类型的肌腱中提取的胶原原纤维的结构（位置与能量储存）在拉伸过程中如何变化并最终失效的完整图景。我们的发现将应用于生物医学领域，在那里肌腱损伤的新治疗方法，以及其他软组织创伤，可以从了解胶原原纤维机械损伤的分子性质和决定因素中受益。为此，我已经与新斯科舍省组织库取得了联系，以确保将研究成果及时翻译给临床医生。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。

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.