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

Bharathan, N. K.; Giang, W.; Chen, E.; Zimmer, S. E.; Lhamo, S.; Jorgens, D. M.; Inman, J. L.; Mennella, V.; Auer, M.; Kowalczyk, A. P.

doi:10.64898/2026.01.27.702185

bioRxiv · 10.64898/2026.01.27.702185

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

Bharathan, N. K.·Giang, W.·Chen, E.·Zimmer, S. E.·Lhamo, S.·Jorgens, D. M.·Inman, J. L.·Mennella, V.·Auer, M.·Kowalczyk, A. P.

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Abstract

Desmosomes are a type of cell-cell adhesive junction present in cardiac tissue and epithelial tissues such as the epidermis. These intercellular junctions anchor to the intermediate filament cytoskeleton, providing mechanical integrity to the tissues in which they reside. 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 and S1 human mammary epithelial cells. We also reveal differences in desmosome ultrastructure at homo- and heterotypic junctions of human nasal airway epithelial cells. Quantitative analyses of these volume EM datasets reveal variations in desmosome size, shape, and organization. Importantly, we report the presence of discontinuities or "holes" within the desmosome outer dense plaque, a novel feature that is observed in either one or both halves of a desmosome. 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.

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Bharathan, N. K., Giang, W., Chen, E., Zimmer, S. E., Lhamo, S., Jorgens, D. M., Inman, J. L., Mennella, V., Auer, M., Kowalczyk, A. P.. 2026-01-30. Volume EM reveals three-dimensional architecture of the desmosome in epithelial cells and tissue models. https://doi.org/10.64898/2026.01.27.702185

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