The newly developed method, cryo-electron microscopy of vitreous sections, was used to observe the nanostructure of the epidermal extracellular space. The data were obtained from vitreous sections of freshly taken, fully hydrated, non-cryo-protected human skin. The extracellular space of viable epidermis contains desmosomes, expressing a characteristic extracellular transverse approximately 5 nm periodicity, interconnected by a relatively electron lucent inter-desmosomal space. The extracellular space between viable and cornified epidermis contains transition desmosomes at different stages of reorganization interconnected by widened areas expressing a rich variety of complex membrane-like structures. The extracellular space of cornified epidermis contains approximately 9, approximately 14, approximately 25, approximately 33, approximately 39, approximately 44, and approximately 48 nm thick regions in turn containing one, two, four, six, eight, eight, and ten parallel electron-dense lines, respectively, between adjacent corneocyte lipid envelopes. The eight-line approximately 44 nm thick regions are most prevalent.
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