The matrix formed by cultures expressing mutant COMP is disturbed. Chondrocytes were fixed after 2 weeks of alginate culture following adenoviral transduction with 20 MOI (a) or 200 MOI (b–d). Electron microscopy of the pericellular matrix of cultures expressing low levels of mutant COMP reveals electron-dense amorphous aggregates (arrow) and some sparse collagen fibrils (a, arrowhead). The matrix formed after transduction with 200 MOI of the vector carrying the gene for mutant COMP has a similar structure, with amorphous aggregates (arrows) and thin collagen fibrils (arrowheads) lacking the regular proteoglycan stain (b). (c) Immunogold-labeling reveals a high concentration of COMP labeling in the amorphous aggregates compared with the low concentration next to the collagen fibers (arrowheads). (d) Chondrocytes overexpressing wild-type COMP form thick collagen fibers (arrow) carrying abundant electron-dense nodular structures (arrowheads). (e) The matrix formed by untransduced chondrocytes shows abundant thick collagen fibers (arrow) with occasional nodular structures corresponding to proteoglycans (arrowheads). Bars, 100 nm.