Review
The structure and function of the stratum corneum

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Abstract

Over the past 150 years the skin's structure and function has been the subject of much investigation by scientists. The stratum corneum (SC), the skin's outermost layer and interface with the outside world is now well recognized as the barrier that prevents unwanted materials from entering, and excessive loss of water from exiting the body. This review summarizes the major advances in our understanding of this formidable membrane. The structure of the SC is outlined as well as techniques to visualize the barrier. The lipid organization and ionic gradients, as well as the metabolic responses and underlying cellular signalling that lead to barrier repair and homeostasis are discussed. Finally, a brief overview of the molecular and genetic factors that determine the development of a competent permeability barrier is provided.

Section snippets

Introduction and historical background

The multilamellar structure of skin has been of interest to scientists since the 19th century. The early work of Homalle (1853) followed by Duriau (1856) recognized that skin layers, and specifically the epidermis and dermis, had different degrees of permeability. In a series of studies from 1924 to 1929, Hermann Rein was the first to demonstrate the presence of a barrier between the stratum corneum (SC) and viable epidermis based on the physiological behaviour of isolated human skin (Rein, 1924

Structure of the stratum corneum

The stratum corneum has an elegantly simple two-compartment structural organization at the light microscopic level, with the corneocytes embedded in a lipid matrix, as visualized by frozen sections, swollen in alkaline buffer and stained with a dye (Christophers and Kligman, 1964), or when stained with Nile red, a fluorescent lipid stain (Simonetti et al., 1995). This prompted its comparison to a “brick and mortar system” (Fig. 1) originally described by Michaels et al. (1975). At the

Visualization tools to study the SC

The major visualization techniques to study the SC to date may be classified as follows:

  • a)

    Optical microscopy. Conventional light and fluorescence microscopy confirmed the basic concept of lipids being sequestered into the extracellular spaces surrounding corneocytes, as well as the progressive change in the profile of lipids from the base to the top of the stratum corneum (Brody, 1989, Veiro and Cummins, 1994). Laser confocal and two photon microscopy used in conjunction with a vast array of

Current understanding of skin barrier function

Skin provides barriers to diverse physical and chemical stressors that it encounters in the environment, including xenobiotics originating from industrial, agricultural and recreational activities. As skin is not just the limiting boundary layer; but also our interface with the habitat, it functions as a dynamic feature rather than a fixed, inflexible barrier layer, as several recent reviews and books have emphasized (Elias and Feingold, 2006, Tobin, 2006, Menon and Kligman, 2009). Its fine

Genes that regulate skin barrier formation

In this era of molecular biology, there has been a huge interest in identifying the genes that control development in general, and skin differentiation in particular, with a view to understanding the skin diseases and dysfunctions that are a consequence of a defective permeability barrier. Knock-out mouse models are one of the most convenient ways to study the effects of single gene deletions, loss of function or gain of function mutations on the skin barrier. The newborn animals are easily

Barrier repair—skin as an actively smart tissue

As the skin barrier is constantly exposed to changing environmental stressors, the SC and underlying epidermis must constantly be sensing, and responding to diverse stimuli, a fact not readily apparent from the static images one sees in a histological slide. The wound healing response of the epidermis, is perhaps one of the most visible manifestations of this adaptation, along with changes in pigmentation that accompany UV exposure. The invisible adaptations in the barrier are measured by

Conclusions and outlook

Advances in our understanding of the skin and primary barrier component, the SC, have been reviewed. The major visualization tools which have lead to our current knowledge are highlighted and the essential role of lipids has also been considered. Regulation of skin barrier formation and response to experimental perturbation underlines the dynamic nature of the SC. The major challenge for the industry is extrapolating from various skin models used for human applications (SC membranes, cadaver

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