Measurement of the biomechanical function and structure of ex vivo drying skin using raman spectral analysis and its modulation with emollient mixtures.

An important aspect of the biomechanical behaviour of the stratum corneum (SC) is the drying stresses that develop with water loss. These stresses act as a driving force for damage in the form of chapping and cracking. Betasitosterol is a plant sterol with a structure similar to cholesterol, a key component in the intercellular lipids of the outermost layer of human skin, the SC. Cholesterol plays an important role in stabilizing the SC lipid structure, and altered levels of cholesterol have been linked with SC barrier abnormalities. Betasitosterol is currently applied topically to skin for treatment of wounds and burns. However, it is unknown what effect betasitosterol has on the biomechanical barrier function of skin. Here, by analysing the drying stress profile of SC generated during a kinetics of dehydration, we show that betasitosterol, in combination with two emollient molecules, isocetyl stearoyl stearate (ISS) and glyceryl tri-2-ethylhexanoate (GTEH), causes a significant modulation of the drying stress behaviour of the SC by reducing both the maximal peak stress height and average plateau of the drying stress profile. Raman spectra analyses demonstrate that the combination of betasitosterol with the two emollients, ISS and GTEH, allows a high water retention capacity within the SC, while the lipid conformational order by increasing the amount of trans conformers. Our study highlights the advantage of combining a biomechanical approach together with Raman spectroscopy in engineering a suitable combination of molecules for alleviating dryness and dry skin damage.

Understanding age-induced alterations to the biomechanical barrier function of human stratum corneum.

BACKGROUND: The appearance and function of human skin are dramatically altered with aging, resulting in higher rates of severe xerosis and other skin complaints. The outermost layer of the epidermis, the stratum corneum (SC), is responsible for the biomechanical barrier function of skin and is also adversely transformed with age. With age the keratin filaments within the corneocytes are prone to crosslinking, the amount of intercellular lipids decreases resulting in fewer lipid bilayers, and the rate of corneocyte turnover decreases. OBJECTIVES: The effect of these structural changes on the mechanical properties of the SC has not been determined. Here we determine how several aspects of the SC's mechanical properties are dramatically degraded with age. METHODS: We performed a range of biomechanical experiments, including micro-tension, bulge, double cantilever beam, and substrate curvature testing on abdominal stratum corneum from cadaveric female donors ranging in age from 29 to 93 years old. RESULTS: We found that the SC stiffens with age, indicating that the keratin fibers stiffen, similarly to collagen fibers in the dermis. The cellular cohesion also increases with age, a result of the altered intercellular lipid structure. The kinetics of water movement through the SC is also decreased. CONCLUSIONS: Our results indicate that the combination of structural and mechanical property changes that occur with age are quite significant and may contribute to the prevalence of skin disorders among the elderly.

The relationship between water loss, mechanical stress, and molecular structure of human stratum corneum ex vivo.

Proper hydration of the stratum corneum (SC) is important for maintaining skin's vital functions. Water loss causes development of drying stresses, which can be perceived as 'tightness', and plays an important role in dry skin damage processes. However, molecular structure modifications arising from water loss and the subsequent development of stress has not been established. We investigated the drying stress mechanism by studying, ex vivo, the behaviors of the SC components during water desorption from initially fully hydrated samples using Raman spectroscopy. Simultaneously, we measure the SC mechanical stress with a substrate curvature instrument. Very good correlations of water loss to the mechanical stress of the stratum corneum were obtained, and the latter was found to depend mainly on the unbound water fraction. In addition to that, the water loss is accompanied with an increase of lipids matrix compactness characterized by lower chain freedom, while protein structure showed an increase in amount of α-helices, a decline in α-sheets, and an increase in folding in the tertiary structure of keratin. The drying process of SC involves a complex interplay of water binding, molecular modifications, and mechanical stress. This article provides a better understanding of the molecular mechanism associated to SC mechanics.

Solar UV radiation reduces the barrier function of human skin.

The ubiquitous presence of solar UV radiation in human life is essential for vitamin D production but also leads to skin photoaging, damage, and malignancies. Photoaging and skin cancer have been extensively studied, but the effects of UV on the critical mechanical barrier function of the outermost layer of the epidermis, the stratum corneum (SC), are not understood. The SC is the first line of defense against environmental exposures like solar UV radiation, and its effects on UV targets within the SC and subsequent alterations in the mechanical properties and related barrier function are unclear. Alteration of the SC's mechanical properties can lead to severe macroscopic skin damage such as chapping and cracking and associated inflammation, infection, scarring, and abnormal desquamation. Here, we show that UV exposure has dramatic effects on cell cohesion and mechanical integrity that are related to its effects on the SC's intercellular components, including intercellular lipids and corneodesmosomes. We found that, although the keratin-controlled stiffness remained surprisingly constant with UV exposure, the intercellular strength, strain, and cohesion decreased markedly. We further show that solar UV radiation poses a double threat to skin by both increasing the biomechanical driving force for damage while simultaneously decreasing the skin's natural ability to resist, compromising the critical barrier function of the skin.