Skin barrier structure, function and formation - learning from cryo-electron microscopy of vitreous, fully hydrated...

The hydration level of the stratum corneum largely depends on the physical state and molecular organization of the stratum corneum intercellular lipid matrix. A better understanding of stratum corneum lipid organization may thus aid the development of more rational cosmetic formulations. Several experimental and theoretical problems of a fundamental character remain, however, unresolved. These are, e.g. that precise quantitative skin barrier compositional data are difficult to obtain and that in vitro experimental skin barrier models usually are of limited value because of the prevailing non-equilibrium conditions in vivo. However, new experimental methods have recently been developed, which may help to overcome some of these limitations. These are, e.g. direct electrospray ionization-mass spectrometry (ESI-MS) of intact long-chain skin ceramides and direct high-resolution cryo-transmission electron microscopy (cryo-TEM) of vitreous sections of native, fully hydrated epidermis. Here, we show that cryo-transmission electron micrographs of vitreous normal human skin often dramatically differ from those obtained by conventional electron microscopy of resin-embedded skin. Our epidermal cryo-TEM data are subsequently discussed in relation to central problems of present conceptions of skin barrier structure, function and formation.