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：提供机械稳定性和实现无缝移动。肌腱损伤非常常见，并且难以成功治疗，部分原因是对机械载荷如何通过肌腱内的结构传递的理解有限。大规模施加的力向下传递到细胞水平，从而改变肌腱的生物反应。不幸的是，目前还不清楚复杂的肌腱结构中的哪些组件负责力传递。在最小的层面上，肌腱有长的胶原蛋白分子通过其他分子连接在一起，其中一组是柔性的，另一组是非常刚性的。 胶原蛋白分子之间刚性和柔性连接的相对数量决定了肌腱的强度和刚度。 然而，这两种类型的分子键如何相互作用，使肌腱的机械强度和刚度还没有得到正确的理解。 这种知识上的差距使得很难完全确定健康的肌腱如何发挥作用以及它们的力传递能力在受伤后如何变化。 该项目将测量具有不同数量的两种连接器类型的肌腱的特性，并从分子水平创建肌腱模型，以了解它如何在非常基本的水平上机械地发挥作用。 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。该研究项目包括一些教育目标。 其中之一是建立一个互动的课堂部分，介绍力学在理解K-12观众的生物材料方面的重要性，以吸引学生进入STEM领域。另一个是改善研究生生物力学课程使用多尺度力学的基本概念，如在本研究项目中使用。 改进后的课程中的先进材料将培训继续该领域研究所需的下一代科学家。本项目的目的是确定肌腱力学中两种特定连接成分的作用：酶促胶原交联和弹性纤维。这些组织成分对于肌腱中的机械载荷承载是重要的，但是它们如何改变机械特性还没有详细的了解。该项目将使用实验和计算相结合的方法来确定这些连接组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来评价改变的胶原交联和受损的弹性纤维组装的动物模型。实验将补充胶原蛋白网络计算模型，以确定连接组件的单独和耦合的机械效应，并评估跨长度尺度的力传递假设。这项研究将大大提高对以下问题的理解：（1）基本肌腱力学，包括连接元件在结构水平上的作用;（2）连接元件之间的互补或耦合相互作用的影响;（3）连接元件的数量/类型如何改变导致机械功能受损;和（4）对连接组分进行受控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提供了一个很好的系统来研究延伸到其他软组织的基本关系。这些概念还可以激发材料设计的新想法，并启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.