Defining the Role of Elastic Fibers in Tendon Mechanics

定义弹性纤维在肌腱力学中的作用

• 批准号: 2037125
• 负责人: Spencer Lake
• 金额: $ 45.43万
• 依托单位: Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2037125&HistoricalAwards=false
• 关键词: Defining; Role; Elastic; Fibers; Tendon

Tendons are essential tissues that transfer mechanical forces between muscles and bones. This allows movement of the body and increases stability. Collagen is the main component of tendon, and collagen is well-aligned with the tensile forces that tendons are subjected to during use. However, other components of tendon also aid in its function. Of these other components, elastic fibers are known to affect how tendons respond to mechanical forces. When elastic fibers in tendon are damaged or degraded, chronic pain or injuries can develop. However, it remains unclear how elastic fibers contribute to the mechanical properties of tendon and how they respond to repetitive use. This project will address this important gap in knowledge by investigating the role of elastic fibers in tendon under a broad range of conditions. Information gained from this research will advance understanding of how tendons function under healthy conditions. This may eventually lead to improved strategies to treat or replace tendons that have damaged or degraded elastic fibers to restore function and reduce the burden associated with these conditions. This project will also develop a workshop on novel 3D tissue imaging to broaden impact within local research communities as well as partner with a high school biomedical science program to provide unique educational opportunities to aspiring scientists/engineers.The objective of this research is to define the role of elastic fibers in tendon mechanics. Elastic fibers are a structural constituent of the tendon extracellular matrix and are therefore necessary for its mechanical integrity. Despite the evidence demonstrating the importance of elastic fibers in maintaining healthy mechanical properties in tendon, the detailed contributions of elastic fibers in tendon mechanics are not yet understood. This research will determine how elastic fibers affect the mechanical function of tendon by comparing the base structure, composition, and mechanics of normal and elastin-null mouse tendons using an array of experiments including two-photon and transmission electron microscopy, biochemical assays, and mechanical testing. The role of elastic fibers in overuse-induced tendinopathy will be determined using fatigue testing and forced treadmill running using mice to induce damage, while testing of cultured tendon explants will inform potential effects of elastic fibers on mechanotransduction. In addition, enzymatic degradation of elastic fibers in tendon will be utilized to evaluate the distinct roles of elastic fibers within fascicles and within the interfascicular matrix. Conclusions from this work will advance understanding of composition-dependent mechanics in tendon and ultimately inform efforts to restore proper function in tendons with elastinopathic conditions or with degradation caused by overuse or age. This work is co-funded by the Biomechanics & Mechanobiology and the Physiological Mechanisms & Biomechanics programs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

肌腱是在肌肉和骨骼之间传递机械力的重要组织。 这允许身体运动并增加稳定性。胶原蛋白是肌腱的主要成分，并且胶原蛋白与肌腱在使用期间所经受的张力很好地对齐。 然而，肌腱的其他成分也有助于其功能。在这些其他成分中，已知弹性纤维会影响肌腱对机械力的反应。当肌腱中的弹性纤维受损或降解时，可能会出现慢性疼痛或损伤。然而，目前尚不清楚弹性纤维如何影响肌腱的机械性能以及它们如何对重复使用做出反应。该项目将通过研究弹性纤维在广泛条件下在肌腱中的作用来解决这一重要的知识空白。从这项研究中获得的信息将促进对肌腱在健康条件下如何发挥作用的理解。这可能最终导致改进的策略来治疗或替换已经损坏或退化的弹性纤维的肌腱，以恢复功能并减少与这些疾病相关的负担。 该项目还将开发一个关于新型3D组织成像的研讨会，以扩大在当地研究社区的影响，并与高中生物医学科学计划合作，为有抱负的科学家/工程师提供独特的教育机会。弹性纤维是肌腱细胞外基质的结构组成部分，因此对于其机械完整性是必需的。尽管有证据表明弹性纤维在维持肌腱健康力学性能方面的重要性，但弹性纤维在肌腱力学中的详细贡献尚未被理解。这项研究将通过比较正常和无弹性蛋白小鼠肌腱的基础结构，组成和力学，确定弹性纤维如何影响肌腱的机械功能，使用一系列实验，包括双光子和透射电子显微镜，生化测定和机械测试。弹性纤维在过度使用诱导的肌腱病中的作用将使用疲劳测试和使用小鼠强制跑步机跑步以诱导损伤来确定，而培养的肌腱外植体的测试将告知弹性纤维对机械转导的潜在影响。此外，肌腱中弹性纤维的酶促降解将用于评估弹性纤维在束内和束间基质内的不同作用。这项工作的结论将促进对肌腱成分依赖性力学的理解，并最终为恢复弹性蛋白病条件下肌腱或过度使用或年龄引起的退化的正常功能提供信息。 这项工作由生物力学机械生物学和生理机制生物力学计划共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Quantative MRI predicts tendon mechanical behavior, collagen composition, and organization.

定量 MRI 可预测肌腱的机械行为、胶原蛋白成分和组织。

• DOI: 10.1002/jor.25471
• 发表时间: 2023
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Zellers,JenniferA;Edalati,Masoud;Eekhoff,JeremyD;McNish,Reika;Tang,SimonY;Lake,SpencerP;Mueller,MichaelJ;Hastings,MaryK;Zheng,Jie
• 通讯作者: Zheng,Jie

Fascicular elastin within tendon contributes to the magnitude and modulus gradient of the elastic stress response across tendon type and species

肌腱内的束状弹性蛋白有助于跨肌腱类型和物种的弹性应力响应的幅度和模量梯度

• DOI: 10.1016/j.actbio.2022.03.025
• 发表时间: 2023
• 期刊: Acta Biomaterialia
• 影响因子: 9.7
• 作者: Eekhoff, Jeremy D.;Abraham, James A.;Schott, Hayden R.;Solon, Lorenzo F.;Ulloa, Gabriella E.;Zellers, Jennifer A.;Cannon, Paul C.;Lake, Spencer P.
• 通讯作者: Lake, Spencer P.

Three-dimensional computation of fibre orientation, diameter and branching in segmented image stacks of fibrous networks

• DOI: 10.1098/rsif.2020.0371
• 发表时间: 2020-08-26
• 期刊: JOURNAL OF THE ROYAL SOCIETY INTERFACE
• 影响因子: 3.9
• 作者: Eekhoff, Jeremy D.;Lake, Spencer P.
• 通讯作者: Lake, Spencer P.