Multiscale Mechanisms of Force Transfer in Tendon

肌腱是连接肌肉和骨骼的软组织，为关节提供两个关键功能：提供机械稳定性和无缝移动。肌腱损伤非常常见，并且很难成功治疗，部分原因是对机械载荷如何通过肌腱内部结构转移的理解有限。大规模施加的力会传递到细胞水平，从而改变肌腱的生物学反应。不幸的是，目前尚不清楚复杂肌腱结构中的哪些成分负责力传递。在最小的层面上，肌腱有长长的胶原蛋白分子，这些胶原蛋白分子由其他分子连接在一起，其中一组是柔韧的，另一组是相当坚硬的。胶原蛋白分子之间的刚性和柔性连接的相对数量决定了肌腱的强度和硬度。然而，这两种类型的分子键是如何相互作用使肌腱在机械上变得坚固和僵硬的，还没有得到很好的理解。这种知识上的差距使得完全确定健康肌腱的功能以及受伤后其力量传递能力的变化变得困难。该项目将测量含有不同数量的这两种连接体的肌腱的特性，并从分子水平建立一个肌腱模型，以便在非常基本的水平上了解它的机械功能。更好的肌腱模型有可能通过减少与肌腱损伤相关的疼痛、残疾和医疗费用来造福社会。这个研究项目包括一些教育目标。其中包括为K-12学生建立一个关于力学在理解生物材料方面的重要性的互动课堂部分，以吸引学生进入STEM领域。另一个目标是利用本研究项目中使用的多尺度力学的基本概念来改进研究生生物力学课程。改进课程中的先进材料将培养继续在该领域进行研究所需的下一代科学家。该项目的目的是确定两种特定的连接成分在肌腱力学中的作用：酶促胶原交联和弹性纤维。这些组织成分对肌腱的机械载荷承载很重要，但是它们如何改变机械性能还没有详细的了解。本项目将采用实验和计算相结合的方法来确定这些连接部件在肌腱中的多尺度力学作用。将使用生物力学测试结合双光子显微镜和偏振光成像对胶原交联改变和弹性纤维组装受损的动物模型进行评估。实验将辅以胶原蛋白网络计算模型，以确定连接组件的单个和耦合力学效应，并评估跨长度尺度力传递的假设。本研究将极大地提高对以下方面的理解：(1)基本肌腱力学，包括跨结构层连接部件的作用；(2)连接要素之间的互补或耦合作用；(3)连接部件数量/类型的改变如何导致机械功能受损；(4)对连接成分进行控制修饰以防止组织损伤或损伤进展的潜在治疗应用。实验方法和计算框架为研究扩展到其他软组织的基本关系提供了一个很好的系统。这些概念还可以激发材料设计的新想法，并激发思考多尺度材料的力传递和组装的新方法。

Tendons are soft tissues that connect between muscles and bones to serve two key functions for joints: provide mechanical stability and enable seamless mobility. Tendon injuries are very common and are difficult to treat successfully, in part because of the limited understanding of how mechanical loads transfer through the structures within tendons. Forces applied at the large-scale are transmitted down to the level of cells, which changes the tendon responds biologically. Unfortunately, it remains unclear which components within the complex tendon structure are responsible for force transfer. At the smallest level a tendon has long collagen molecules connected together by other molecule one group of which is flexible and another that is quite stiff. The relative amount of stiff and flexible connections between the collagen molecules determines how strong and stiff the tendon is. However, how the two types of molecular linkages interact to make the tendon strong and stiff mechanically is not properly understood. This gap in knowledge has made it difficult to completely determine how healthy tendons function and how their force-transmission capabilities change after injury. The project will measure the properties of tendons with different amounts of the two linker types and create a model of the tendon built up from the molecular level in order to understand how it functions mechanically at a very basic level. The better model for the tendon has the potential to benefit society by reducing pain, disability, and healthcare costs associated with tendon injuries. This research project includes a number of educational goals. Among them is to build an interactive class section on how mechanics is important in understanding biological materials for a K-12 audience to attract students into STEM fields. Another is to improve a graduate biomechanics course using fundamental concepts of multi-scale mechanics such as are used in this research project. The advanced material in that improved course will train the next generation of scientists needed to continue research in the area. The objective of this project is to determine the role of two specific linking components in tendon mechanics: enzymatic collagen crosslinks and elastic fibers. These tissue constituents are important for mechanical load carriage in tendon, however how they change mechanical properties is not understood in a detailed way. This project will use a combined experimental and computational approach to determine the multiscale mechanical role of these linking components in tendon. Animal models of altered collagen crosslinks and impaired elastic fiber assemblies will be evaluated using biomechanical testing combined with two-photon microscopy and polarized light imaging. Experiments will be complemented with a collagen network computational model to determine individual and coupled mechanical effects of linking components, and evaluate hypotheses on force transmission across length scales. This study will greatly improve understanding of: (1) fundamental tendon mechanics, including the role of linking components across structural levels; (2) effects of complementary or coupled interactions between linking elements; (3) how altered quantities/types of linking components lead to impaired mechanical function; and (4) potential therapeutic applications of controlled modifications to linking components to prevent tissue damage or injury progression. The experimental approach and computational framework provide an excellent system to study fundamental relations that extends to other soft tissues. These concepts could also motivate new ideas in material design and inspire new ways to think about force transfer and assembly of multiscale materials.