Volume EM reveals desmosome three-dimensional architecture in epithelial cells and tissue models

Desmosomes are cell–cell adhesive junctions present in cardiac tissues and epithelial tissues such as the epidermis. These junctions anchor to the intermediate filament cytoskeleton, providing mechanical integrity. Our understanding of desmosome architecture has largely been influenced by observations of two-dimensional images obtained through conventional electron microscopy. Here, using focused ion beam scanning electron microscopy, we report the three-dimensional ultrastructure of desmosomes in A431 epidermoid carcinoma and S1 human mammary epithelial cells. We also reveal differences in desmosome ultrastructure at homotypic and heterotypic junctions of human airway epithelial cells. Quantitative analyses of these datasets reveal variations in desmosome size, shape, and organization. Importantly, we report the presence of discontinuities or “gaps” within the outer dense plaque, a novel feature observed in either one or both desmosome halves. This study provides the first comprehensive description of the epithelial desmosome as a three-dimensional structure and emphasizes the need to investigate the effects of dynamic morphogenetic processes and disease states on desmosome ultrastructure.