Multimodal Failure Mechanics in the Collagen Fibril

胶原原纤维的多模式失效机制

• 批准号: RGPIN-2016-05267
• 负责人: Lee, Michael
• 金额: $ 2.04万
• 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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=709629
• 关键词: Multimodal; Failure; Mechanics; Collagen; Fibril

Collagen's evolutionary longevity is a tribute to the survival value of its complex, self--assembled structure. While both elasticity and overload damage have been studied extensively at the light microscope level in connective tissues, it is below that scalereally at the nanometer scalewhere mechanical load is borne. It is there that collagen's strength is achievedand perhaps more important for survival, where its toughness is determined. For the last 10 years or so, I have been interested in two fundamental questions: (i) What does mechanical damage in collagen look like at its most fundamental levels? (ii) Are there structural motifs for damage in collagen that activate physiologically appropriate cellular repair or replacement? These are questions of deep import for understanding the biomechanical evolution of the collagen fibril and for rational design of processed collagen products which can mimic native toughness and modulate inflammation and healing. We recently demonstrated that overloading of tendon collagen produces a characteristic, local, nano-scaled “kinking” of collagen fibrils (5200 nm dia.). Fibril-level damage leads to thermodynamic instability of the packed collagen molecules, consistent with local denaturation. Enzymolysis and very high magnification SEM (50-70kX) of overloaded tendons have shown that a sub-set (only) of the sub-fibrils at the kink zones are disrupted while others remain. Repeated plastic overload without rupture produces a linear densification of the kinks along individual damaged fibrils. The collagen fibril has thus been revealed to be unexpectedly heterogeneous: both across its diameter and along its length. We have a working theory that the local “kink” failure mechanism has 2--way evolutionary value: toughening tissues like tendons to prevent catastrophic failure while providing the structural cues that guide resorption and/or repair of damaged fibrils. I believe this knowledge can be used. I propose to further explore the fundamental structuro--mechanical questions which have emerged from our work to date, applying SEM, cryo-TEM, and AFM plus finer-scale, stretch-retained samples to reduce heterogeneity of damage, thereby visualizing kink zone failures before elastic rebound. We will also produce laboratory-extruded collagen fibres to study the extent to which the heterogeneous fibril assembly necessary to the discrete plasticity mechanism is innate to collagen, and what interventions must be applied to produce it for technological value. Finally, we will study the question of whether the serial kink zones which form in damaged fibrils are periodic in nature or stochastically determined. With that knowledge, we will explore fibril-to-fibril propagation of kink formation and seek to produce a model which can couple nanoscale molecular/fibril damage to micron-scale fibre failure.

胶原蛋白的进化寿命是对其复杂，自组装结构的生存价值的致敬。虽然在连接时间的光显微镜水平上对弹性和过载损伤都进行了广泛的研究，但在机械负载的纳米尺度上，它却低于该尺寸。在那里，胶原蛋白的力量是可以实现的，对于确定其韧性的生存可能更为重要。在过去的十年左右的时间里，我一直对两个基本问题感兴趣： （i）胶原蛋白的机械损害在其最基本的水平上是什么样的？ （ii）在胶原蛋白中是否有结构性基序可激活物理适当的细胞修复或置换？这些问题是了解胶原原纤维的生物力学演化以及加工后的胶原蛋白产品的合理设计，这些问题可以模仿天然韧性并调节注射和愈合。 我们最近证明，肌腱胶原蛋白的过载产生了胶原原纤维（直径5200 nm）的特征性，局部，纳米尺度的“扭结”。原纤维水平的损伤导致堆积的胶原蛋白分子的热力学不稳定性与局部变性一致。酶解和非常高的放大倍数（50-70kx）的过肌肌腱表明，扭结区域处的亚元素的子集（仅）被中断，而其他子则剩下。反复的塑料过载而不破裂会产生沿个体损伤原纤维的扭结线性致密化。因此，胶原原纤维已被揭示出意外的异质性：跨直径和沿其长度。我们有一个工作理论，即局部的“扭结”故障机制具有2个 - 进化价值：加强组织，例如肌腱，以防止灾难性失败，同时提供指导损坏原纤维的解析和/或修复的结构线索。我相信可以使用这些知识。 我建议进一步探索迄今为止我们的工作中出现的基本结构问题 - 应用SEM，Cryo-Tem和AFM以及更精细的，伸展的样品，以减少损害的异质性，从而可视化弹性回弹之前的链球区域失败。我们还将生产实验室脱颖而出的胶原蛋白纤维，以研究离散可塑性机制所必需的异质原纤维组件对胶原蛋白的天生，并且必须采用哪些干预措施来生产它以获得技术价值。最后，我们将研究一个问题，即在损坏的原纤维中形成的串行扭结区域本质上是周期性的还是随机确定的。有了这些知识，我们将探索扭结形成的原纤维到原纤维的传播，并试图产生一个模型，该模型可以将纳米级分子/原纤维损伤与微米尺度纤维衰竭相结合。