New paradigms for relating the microstructure of cartilage to its large scale mechanics: The Roles of Rigidity-Percolation and Double Gel Network Structure in Non-Linear Response

软骨是一种覆盖着关节骨骼的光滑组织，是一种非凡的材料，可以持续数十年，在其独特的材料特性组合上超过任何人造物质。软骨的微观结构有几个方面对其寿命有贡献。首先，产生这些机械性能的基质由两个相互穿透的聚合物网络组成，这种设计最近被证明可以抑制裂缝的形成。其次，软骨的机械性能随深度变化，因此能量衰减几乎完全发生在其表面附近的薄层区域。PI最近开发了一个理论模型，解释了聚合物网络浓度的变化如何导致能量吸收到组织表面的这种局部化。该项目使用一系列实验技术来测试这一模型，并将其适用范围扩展到软骨可能受损的极端变形。通过对组织进行化学处理，去除必要的分子成分，并在没有分子成分的情况下测试组织的反应，PI将确定基质中的哪些元素对于产生软骨独特的机械性能组合是必不可少的。更好地了解软骨力学性能的大分子起源将有助于深入了解关节炎等疾病的发展，指导组织修复治疗的方法，更广泛地说，将为制造能够承受极端载荷的坚固材料提供机械设计标准。关节软骨具有独特的材料特性，使其能够承受每年数百万次的载荷循环，同时保护底层组织。其压缩性能的结构和成分来源几十年来一直是已知的。然而，对于与其剪切行为相关的潜在机制，还没有相应的理解。最近，研究人员引入了刚性渗流理论，该理论以前是用来解释重组聚合物网络的性质的，用来解释软骨剪切力学的线性响应。这一理论认为，观察到的软骨剪切模数量级的变化是由接近刚性渗流阈值的基质成分的微小浓度差异引起的。此外，该理论对非线性剪切行为的分子机制做出了新的预测，并对生物化学和机械损伤引起的力学变化提供了新的见解。该项目将验证这些预测，并确定刚性渗流是否可以作为关节软骨机械剪切特性的大分子起源的新范例。具体地说，使用化学和机械降解技术，将测试该模型对导致软骨宏观力学性能的关键细胞外基质元素的预测。最后，这个项目将扩展模型的适用性，以描述当软骨被剪切超过线性区域时，软骨的微观结构是如何改变的。

Cartilage, the smooth tissue that coats bones in joints, is a remarkable material that can last decades and outperform any man-made substance in its unique combination of material properties. There are several aspects of cartilage's microstructure that contribute to its longevity. First, the matrix that gives rise to these mechanical properties is comprised of two interpenetrating polymer networks, a design that has recently been shown to inhibit crack formation. Second, the mechanical properties of cartilage change with depth such that energy damping occurs almost entirely in a thin region near its surface. The PIs have recently developed a theoretical model that explains how variations in the concentration of the polymer networks lead to this localization of energy absorption to the tissue surface. This project uses an array of experimental techniques to test this model and extend its applicability to extreme deformations where cartilage can be damaged. By chemically treating the tissue to remove essential molecular components and testing the tissue response in their absence, the PIs will determine which elements of the matrix are essential for generating cartilage's unique combination of mechanical properties. A better understanding of the macromolecular origins of cartilage mechanical properties will give insight into how diseases such as arthritis develop, guide approaches to tissue repair therapies, and more broadly, provide mechanical design criteria for fabrication of robust materials that can endure extreme loading.Articular cartilage has unique material properties that enable it to endure millions of loading cycles per year while protecting underlying tissues. The structural and compositional origins of its compressive properties have been known for decades. However, there is no equivalent understanding of the underlying mechanisms associated with its shear behavior. Recently the investigators introduced a rigidity percolation theory, previously established to explain the properties of reconstituted polymer networks, to explain the linear response of cartilage shear mechanics. This theory is that the observed orders of magnitude variation in the shear modulus of cartilage arises from small concentration differences of matrix constituents that are poised near a rigidity percolation threshold. Furthermore, the theory makes novel predictions about molecular mechanisms of non-linear shear behavior and gives new insight into mechanical changes that occur from biochemical and mechanical damage. This project will test these predictions and determining if rigidity percolation can be used as a new paradigm for the macromolecular origins of the mechanical shear properties of articular cartilage. Specifically, using chemical and mechanical degradation techniques, predictions made by the model about the critical extracellular matrix elements that give rise to cartilage's macroscale mechanical properties will be tested. Finally, this project will extend the applicability of the model to describe how the microscopic structure of cartilage is altered when it is sheared beyond the linear regime.