Multimodal Failure Mechanics in the Collagen Fibril

胶原原纤维的多模式失效机制

基本信息

  • 批准号:
    RGPIN-2016-05267
  • 负责人:
  • 金额:
    $ 2.04万
  • 依托单位:
  • 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

项目摘要

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的自我组装结构的生存价值的致敬。虽然在光学显微镜水平上已经对结缔组织的弹性和过载损伤进行了广泛的研究,但在纳米尺度上,机械载荷是在纳米尺度上承受的。正是在那里,胶原蛋白的强度得到了增强,也许对生存更重要,因为它的韧性决定了。在过去的10年里,我一直对两个基本问题感兴趣: (i)胶原蛋白的机械损伤在最基本的水平上是什么样的? (ii)胶原蛋白中是否存在损伤的结构基序,从而激活生理上适当的细胞修复或替换?这些问题对于理解胶原原纤维的生物力学演变和合理设计可以模拟天然韧性并调节炎症和愈合的加工胶原产品具有重要意义。 我们最近证明,超载的肌腱胶原蛋白产生的特征,局部,纳米级的“扭结”的胶原纤维(5200纳米直径)。原纤维水平的损伤导致压缩的胶原分子的热力学不稳定性,与局部变性一致。过载肌腱的酶法和非常高放大倍数的SEM(50- 70 kX)显示,扭结区的亚原纤维的一个子集(仅)被破坏,而其他的保留下来。反复的塑性过载而不断裂,会使扭结沿沿着单个受损原纤维线性致密化。因此,胶原原纤维显示出出乎意料的异质性:在其直径和沿着其长度。我们有一个工作理论,即局部“扭结”失效机制具有双向进化价值:使肌腱等组织增韧以防止灾难性失效,同时提供引导吸收和/或修复受损原纤维的结构线索。我认为这些知识可以利用。 我建议进一步探索的基本结构-机械问题,已经出现了从我们的工作,到目前为止,应用SEM,cryo-TEM,AFM加上更精细的规模,拉伸保留样品,以减少损伤的异质性,从而可视化扭结区失败之前的弹性反弹。我们还将生产实验室挤出的胶原纤维,以研究离散可塑性机制所需的异质原纤维组装在多大程度上是胶原蛋白所固有的,以及必须应用什么干预措施来生产它以获得技术价值。最后,我们将研究在受损纤维中形成的连续扭结区是周期性的还是随机决定的。有了这些知识,我们将探索扭结形成的原纤维到原纤维传播,并寻求产生一个模型,可以耦合纳米级分子/原纤维损伤微米级纤维故障。

项目成果

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Lee, Michael其他文献

Spry2 does not directly modulate Raf-1 kinase activity in v-Ha-ras-transformed NIH 3T3 fibroblasts
  • DOI:
    10.5483/bmbrep.2010.43.3.205
  • 发表时间:
    2010-03-31
  • 期刊:
  • 影响因子:
    3.8
  • 作者:
    Ahn, Jun-Ho;Eum, Ki-Hwan;Lee, Michael
  • 通讯作者:
    Lee, Michael
Short-term peripheral nerve stimulation ameliorates axonal dysfunction after spinal cord injury
  • DOI:
    10.1152/jn.00839.2014
  • 发表时间:
    2015-05-01
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
    Lee, Michael;Kiernan, Matthew C.;Lin, Cindy S. -Y.
  • 通讯作者:
    Lin, Cindy S. -Y.
A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores.
  • DOI:
    10.1186/s13024-023-00633-4
  • 发表时间:
    2023-06-22
  • 期刊:
  • 影响因子:
    15.1
  • 作者:
    Kang, Moonil;Ang, Ting Fang Alvin;Devine, Sherral A.;Sherva, Richard;Mukherjee, Shubhabrata;Trittschuh, Emily H.;Gibbons, Laura E.;Scollard, Phoebe;Lee, Michael;Choi, Seo-Eun;Klinedinst, Brandon;Nakano, Connie;Dumitrescu, Logan C.;Durant, Alaina;Hohman, Timothy J.;Cuccaro, Michael L.;Saykin, Andrew J.;Kukull, Walter A.;Bennett, David A.;Wang, Li-San;Mayeux, Richard P.;Haines, Jonathan L.;Pericak-Vance, Margaret A.;Schellenberg, Gerard D.;Crane, Paul K.;Au, Rhoda;Lunetta, Kathryn L.;Mez, Jesse B.;Farrer, Lindsay A.
  • 通讯作者:
    Farrer, Lindsay A.
Generative design for COVID-19 and future pathogens using stochastic multi-agent simulation.
  • DOI:
    10.1016/j.scs.2023.104661
  • 发表时间:
    2023-10
  • 期刊:
  • 影响因子:
    11.7
  • 作者:
    Lee, Bokyung;Lau, Damon;Mogk, Jeremy P. M.;Lee, Michael;Bibliowicz, Jacobo;Goldstein, Rhys;Tessier, Alexander
  • 通讯作者:
    Tessier, Alexander
Targeting the autophagy pathway using ectopic expression of Beclin 1 in combination with rapamycin in drug-resistant v-Ha-ras-transformed NIH 3T3 cells
  • DOI:
    10.1007/s10059-011-0034-6
  • 发表时间:
    2011-03-01
  • 期刊:
  • 影响因子:
    3.8
  • 作者:
    Eum, Ki-Hwan;Lee, Michael
  • 通讯作者:
    Lee, Michael

Lee, Michael的其他文献

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{{ truncateString('Lee, Michael', 18)}}的其他基金

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
  • 财政年份:
    2021
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Impact of high-intensity interval training on leukocyte migratory potential
高强度间歇训练对白细胞迁移潜能的影响
  • 批准号:
    512987-2017
  • 财政年份:
    2017
  • 资助金额:
    $ 2.04万
  • 项目类别:
    University Undergraduate Student Research Awards
Evaluation of decanoic acid as a neuroprotective agent
癸酸作为神经保护剂的评价
  • 批准号:
    512279-2017
  • 财政年份:
    2017
  • 资助金额:
    $ 2.04万
  • 项目类别:
    University Undergraduate Student Research Awards
Analysis of AICAR as an activator of lactate transport in neuronal cells
AICAR 作为神经元细胞乳酸转运激活剂的分析
  • 批准号:
    498051-2016
  • 财政年份:
    2016
  • 资助金额:
    $ 2.04万
  • 项目类别:
    University Undergraduate Student Research Awards
Failure mechanisms in collagen of heart valves and tissue engineered replacements
心脏瓣膜和组织工程替代品胶原蛋白的失效机制
  • 批准号:
    191922-2010
  • 财政年份:
    2014
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Failure mechanisms in collagen of heart valves and tissue engineered replacements
心脏瓣膜和组织工程替代品胶原蛋白的失效机制
  • 批准号:
    191922-2010
  • 财政年份:
    2013
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Characterization of translation elongation mechanisms
翻译延伸机制的表征
  • 批准号:
    433159-2012
  • 财政年份:
    2012
  • 资助金额:
    $ 2.04万
  • 项目类别:
    University Undergraduate Student Research Awards
Failure mechanisms in collagen of heart valves and tissue engineered replacements
心脏瓣膜和组织工程替代品胶原蛋白的失效机制
  • 批准号:
    191922-2010
  • 财政年份:
    2012
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Failure mechanisms in collagen of heart valves and tissue engineered replacements
心脏瓣膜和组织工程替代品胶原蛋白的失效机制
  • 批准号:
    191922-2010
  • 财政年份:
    2011
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Heat Exchanger and Enclosure Corrosion Improvement
热交换器和外壳腐蚀改善
  • 批准号:
    419070-2011
  • 财政年份:
    2011
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Experience Awards (previously Industrial Undergraduate Student Research Awards)

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Multimodal Failure Mechanics in the Collagen Fibril
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    $ 2.04万
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