Defining the Role of Elastic Fibers in Tendon Mechanics

肌腱是肌肉和骨骼之间传递机械力的重要组织。这允许身体移动，并增加了稳定性。胶原蛋白是肌腱的主要成分，胶原蛋白与肌腱在使用过程中受到的拉力很好地对齐。然而，肌腱的其他组成部分也有助于其功能。在这些其他成分中，众所周知，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力学性能，以及它们对重复使用的反应。这个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。这最终可能导致改进治疗或替换受损或退化的弹性纤维的肌腱的策略，以恢复功能并减轻与这些情况相关的负担。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，并与一个高中生物医学科学项目合作，为有抱负的科学家/工程师提供独特的教育机会。这项研究的目标是确定弹性纤维在肌腱力学中的作用。弹性纤维是肌腱细胞外基质的结构成分，因此是肌腱力学完整性所必需的。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具体作用尚不清楚。这项研究将通过比较正常和弹性蛋白缺失的小鼠肌腱的基本结构、组成和力学性能，使用包括双光子和透射电子显微镜、生化分析和力学测试在内的一系列实验来确定弹性纤维如何影响肌腱的机械功能。弹性纤维在过度使用引起的肌腱病变中的作用将通过疲劳测试和强迫跑步机在小鼠身上造成损伤来确定，而对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，还将利用肌腱中弹性纤维的酶降解来评估弹性纤维在肌束内和肌束间基质中的不同作用。这项工作的结论将促进对肌腱成分依赖的力学的理解，并最终为恢复弹力性疾病或因过度使用或年龄引起的肌腱退化而恢复正常功能的努力提供参考。这项工作由生物力学与机械生物学和生理机制与生物力学项目共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.