Chahine Nadeen O, Hung Clark T, Ateshian Gerard A
Musculoskeletal Biomechanics Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
Eur Cell Mater. 2007 May 31;13:100-11; discussion 111. doi: 10.22203/ecm.v013a11.
Chondrocytes are responsible for the elaboration and maintenance of the extracellular (EC) matrix in articular cartilage, and previous studies have demonstrated that mechanical loading modulates the biosynthetic response of chondrocytes in cartilage explants. The goal of this study is to investigate the deformation behaviour of the chondrocyte and its microenvironment under transient loading, in order to address the relationship between the applied dynamic deformation and cellular strain. In-situ strain measurements were performed on cells in the middle (MZ) zone at early time points during ramp loading and at equilibrium. In this study, we characterized the behaviour of cartilage at the zonal and cellular levels under compressive loading using digital image analysis on miniature samples tested in a custom microscopy-based loading device. The experimental results indicate that significant strain amplification occurs in the microenvironment of the cell, with the minimum (compressive) principal strain found to be nearly 7X higher in the intracellular region (IC), and ~5X higher in the pericellular (PC) matrix than in the EC matrix at peak ramp. A similar strain amplification mechanism was observed in the maximum (tensile) principal strain, and this behaviour persisted even after equilibrium was reached. The experimental results of this study were interpreted in the context of a finite element model of chondrocyte deformation, which modelled the cell as a homogeneous gel, possessing either a spherical or ellipsoidal geometry, surrounded by a semi permeable membrane, and accounted for the presence of a PC matrix. The results of the FEA demonstrate significant strain amplification mechanism in the IC region, greater than had previously been suggested in earlier computational studies of cell-EC matrix interactions. Based on the FEA, this outcome is understood to result from the large disparity between EC matrix and intracellular properties. The results of this study suggest that mechanotransduction of chondrocytes may be significantly mediated by this strain amplification mechanism during loading.
软骨细胞负责关节软骨细胞外（EC）基质的形成和维持，先前的研究表明机械负荷可调节软骨外植体中软骨细胞的生物合成反应。本研究的目的是研究软骨细胞及其微环境在瞬态负荷下的变形行为，以探讨施加的动态变形与细胞应变之间的关系。在斜坡加载早期和平衡时，对中间（MZ）区的细胞进行了原位应变测量。在本研究中，我们使用基于定制显微镜加载装置测试的微型样本上的数字图像分析，在压缩负荷下在区域和细胞水平上表征了软骨的行为。实验结果表明，在细胞微环境中发生了显著的应变放大，在斜坡峰值时，细胞内区域（IC）的最小（压缩）主应变比EC基质中高近7倍，在细胞周（PC）基质中比EC基质中高约5倍。在最大（拉伸）主应变中也观察到类似的应变放大机制，即使在达到平衡后这种行为仍然存在。本研究的实验结果在软骨细胞变形的有限元模型背景下进行了解释，该模型将细胞建模为具有球形或椭圆形几何形状、被半透膜包围并考虑了PC基质存在的均匀凝胶。有限元分析（FEA）结果表明，IC区域存在显著的应变放大机制，比先前细胞-EC基质相互作用的计算研究中所提出的更大。基于有限元分析，这一结果被认为是由于EC基质和细胞内特性之间的巨大差异所致。本研究结果表明，在负荷期间，软骨细胞的机械转导可能由这种应变放大机制显著介导。
