Structure, Mechanics, and Mechanobiology of Fibrocartilage Pericellular Matrix Mediated by Type V Collagen

The pericellular matrix (PCM) is the immediate microniche surrounding cells in various tissues, regulating matrix turnover, cell-matrix interactions, and disease. This study elucidates the structure-mechanical properties and mechanobiology of the PCM in fibrocartilage, using the murine meniscus as the model. The fibrocartilage PCM is comprised of thin, randomly oriented collagen fibrils that entrap proteoglycans, contrasting with the densely packed, highly aligned collagen fibers in the bulk extracellular matrix (ECM). Compared to the ECM, the PCM exhibits lower modulus and greater isotropy, but has similar relative viscoelastic properties. In Col5a1^+/- menisci, the reduction of collagen V results in thicker, more heterogeneous collagen fibrils, reduced modulus, loss of isotropy and faster viscoelastic relaxation in the PCM. Such altered PCM leads to impaired matrix-to-cell strain transmission, and in turn, disrupts mechanotransduction of meniscal cells, as illustrated by reduced calcium signaling activities and alters expression of matrix genes. In vitro, Col5a1^+/- cells produce a weakened PCM with inferior properties and reduced protection of cells against tensile stretch. These findings highlight the PCM as a distinctive microstructure in fibrocartilage mechanobiology, underscoring a pivotal role of collagen V in PCM function. Targeting the PCM or its constituents offers potential for improving meniscus regeneration, osteoarthritis intervention and broader fibrocartilage-related therapies.