The skin barrier : structure and physical function

• The objective of the project "The skin barrier - structure and physical function" was to characterise in detail the human skin barrier structurally and functionally. The thesis work includes in-vivo studies, in-vitro studies and studies on pure model systems. In the pursuit of the thesis work several new techniques and one new skin barrier model system have been developed; (a) a new technique for thickness and area measurements of isolated stratum corneum using confocal laser scanning microscopy (CLSM) and digitising tablet, (b) a new technique for separation and quantitation of stratum corneum lipids using high pressure liquid chromatography with light scattering detection (HPLC/LSD), (c) a new technique for extraction of inner stratum corneum lipids in-vivo, (d) a new technique for measurements of water diffusion through stratum corneum and lipid phases using an Evaporimeter in-vitro, (e) a new skin barrier lipid model system including both crystalline and liquid crystalline phases in equilibrium. The biophysical and analytical techniques that have been employed in addition to those mentioned above include gas chromatography (GC) with flame ionisation detection (FID), mass spectrometry (MS), thin layer chromatography (TLC), X-ray diffraction (SAXD and WAXD), transepidermal water loss TEWL), skin electrical impedance (EI) and capacitance measurements (CM). Also, during my PhD work I have had the opportunity to work briefly with supercritical carbon dioxide extraction and separation (SC-CO2), differential scanning calorimetry (DSC) and atomic force microscopy (AFM). Paper 1 shows that the swelling of the stratum corneum is most pronounced in the thickness dimension and that the corneocytes are permeable to water at a time-scale relevant for water diffusion. Paper 2 and 3 address the crucial problem of the existence of a liquid crystalline structure in the stratum corneum. Paper 2 focus on the stratum corneum free fatty acid fraction and paper 3 discusses the role of cholesterol for the barrier properties. Paper 4 and 5 treat diffusional pathways for water through stratum corneum and through lipid skin barrier model mixtures respectively. A new structural and functional model for the mammalian skin barrier, The "Plastic" Model, is postulated. A single "plastic" structure ([alpha]-form stabilised by cholesterol and "impurities" in hydrocarbon chainlength distributions), with virtually no "phase" borders, is proposed to be directly responsible for the extraordinary barrier capacity of mammalian skin. It is prophesied that the true, intact barrier, i.e., the single "plastic" structure ([alpha]-form), is only located to the lower part of stratum corneum where the water concentration is high, promoting higher degree of alkyl chain rotational disorder. At higher levels of stratum corneum the lipid morphology of the intercellular space becomes more heterogeneous (i.e., "phase" separation occurs) due to (a) lower water concentration (inducing "phase" transitions and "phase" separation) and (b) lipid degrading and recycling processes during cell shedding, and intermixing with sebaceous gland lipids (resulting in suboptimal cholesterol concentrations and introduction of unsaturated and medium chain lipid species).

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