Zonal changes in the three-dimensional morphology of the chondron under compression: The relationship among cellular, pericellular, and extracellular deformation in articular cartilage

Abstract

The pericellular matrix (PCM) is a narrow region of tissue that completely surrounds chondrocytes in articular cartilage. Previous theoretical models of the "chondron" (the PCM with enclosed cells) suggest that the structure and properties of the PCM may significantly influence the mechanical environment of the chondrocyte. The objective of this study was to quantify changes in the three-dimensional (3D) morphology of the chondron in situ at different magnitudes of compression applied to the cartilage extracellular matrix. Fluorescence immunolabeling for type-VI collagen was used to identify the boundaries of the cell and PCM, and confocal microscopy was used to form 3D images of chondrons from superficial, middle, and deep zone cartilage in explants compressed to 0%, 10%, 30%, and 50% surface-to-surface strain. Lagrangian tissue strain, determined locally using texture correlation, was highly inhomogeneous and revealed depth-dependent compressive stiffness and Poisson's ratio of the extracellular matrix. Compression significantly decreased cell and chondron height and volume, depending on the zone and magnitude of compression. In the superficial zone, cellular-level strains were always lower than tissue-level strains. In the middle and deep zones, however, tissue strains below 25% were amplified at the cellular level, while tissue strains above 25% were decreased at the cellular level. These findings are consistent with previous theoretical models of the chondron, suggesting that the PCM can serve as either a protective layer for the chondrocyte or a transducer that amplifies strain, such that cellular-level strains are more homogenous throughout the tissue depth despite large inhomogeneities in local ECM strains.

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage

“…S5). The resulting 50% strain is considered hyperphysiologic and injurious (3,(34)(35)(36). The Ca 2+ transients (Fig.…”

Immunofluorescence-guided atomic force microscopy to measure the micromechanical properties of the pericellular matrix of porcine articular cartilage

“…In particular, the stress -strain environment of the chondrocyte heavily depends on the relative mechanical properties of the chondrocyte, its PCM, and the local ECM [16,17,23]. Cartilage is subdivided into three zones (superficial, middle and deep) based on the depth from the articular surface that are characterized by differences in ECM composition and ultrastructure [14,[25][26][27] and chondrocyte morphology and arrangement [12,28].…”

Depth-dependent refractive index of normal and early degenerated articular cartilage

“…Confocal microscopy was utilized in some studies to measure the tiny deformations of the AC samples applied with various mechanical and biochemical conditions. 6,14,15 However, the RI mismatch between the AC specimen and the confocal system can deform the images along the optical axis. 16 The RI distribution of AC should be considered in such studies to minimize the errors induced by the mismatched RI.…”