Molecular Organization of the Skin Barrier

Cryo-electron microscopy of vitreous sections allows for investigation directly in situ of the molecular architecture of skin. Recently, this technique has contributed to the elucidation of the molecular organization of the skin’s permeability barrier and its stepwise formation process. The aim of this review is to provide an overview of the procedure for cryo-electron microscopy of vitreous sections, its analysis using atomic detail molecular dynamics modelling and electron microscopy simulation, and its application in the investigation of the barrier structure and formation process of the skin. SIGNIFICANCE This review presents the structure, function and formation of the human skin barrier based on high-resolution cryo-electron microscopy. This knowledge can be used to control the barrier function of the skin at the atomic level via computer simulation, enabling drug-transport to and through skin to be calculated and optimized, and barrier deficiency in skin disease to be predicted and investigated on the molecular level.