Development of the mechanoresponsive pericellular matrix of chondrons

Physical properties of cartilage are conferred by the composition and ultrastructure of the extracellular matrix. This study focuses on the development of the pericellular matrix (PCM), a domain that directly contacts the chondrocyte and is a key regulator of biomechanical and biochemical signaling. Using three-dimensional cell culture, microfluidic cell compression platforms, and genetic mouse models, we demonstrated that collagen VI is initially assembled at the cell surface and then displaced to form a shell at the PCM-territorial matrix boundary. Cell surface-bound hyaluronan is crucial for the assembly process, and hyaluronan-aggrecan complexes drive displacement. Integrin adhesion is not required early but is crucial to determine the final placement of the collagen VI shell. Dynamic compression accelerated PCM maturation except in aggrecan mutants. Together, these findings provide key insights into the development of the mechanosensitive PCM and establish an in vitro platform to support studies of matrix biology in normal and disease models.