The Influence of the Chondrocyte Microenvironment on Multiscale Articular Cartilage Mechanics: A Computational Study.

Chondrocytes are mechanosensitive cells whose biosynthetic activity is governed by their local mechanical environment within articular cartilage. This environment is strongly influenced by the pericellular matrix (PCM), a specialized region enriched in collagen VI and a distinct non-fibrillar ground substance. However, the individual mechanical roles of these PCM constituents in regulating chondrocyte mechanotransduction remain poorly understood. In this study, an explicit, concurrent multiscale finite element model of articular cartilage was developed to directly link tissue-level loading to cellular-scale mechanics. The model incorporates anatomically realistic chondrocyte distributions, depth-dependent collagen II fibril architecture, and distinct representations of collagen VI fibrils and the non-fibrillar PCM matrix. Unconfined compression simulations were performed under reference conditions and following targeted alterations (±20%) in collagen VI stiffness, PCM matrix stiffness, or both. Results showed that tissue-level reaction forces were most sensitive to collagen VI stiffness. At the cellular scale, changes in collagen VI and PCM matrix properties significantly modulated chondrocyte circumferential forces and volumetric deformation, particularly in the superficial zone. Stress redistribution analyses revealed a load-sharing mechanism between fibrillar and non-fibrillar PCM components. These findings clarify the distinct mechanical roles of PCM constituents and provide mechanistic insight into how their degradation may disrupt chondrocyte mechanotransduction and contribute to cartilage degeneration.