The lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier function. The three main SC lipid classes are ceramides (CER), cholesterol and... Show moreThe lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier function. The three main SC lipid classes are ceramides (CER), cholesterol and free fatty acids. In inflammatory skin diseases, such as atopic dermatitis and psoriasis, the SC lipid composition is altered compared to the healthy SC composition. The studies presented in this thesis focused on the effect of the CER subclass composition on the lipid organization, molecular arrangement and barrier function of the skin. First, the CER compositional changes were examined in the SC of seborrheic dermatitis patients, an inflammatory skin disease. A particular emphasis was paid to the ratio of two important CER subclasses, sphingosine CER (CER NS) and phytosphingosine CER (CER NP), and its correlation to the skin barrier. In the subsequent chapters lipid model systems with a simple CER subclass composition were used to study the influence of the CER NS: CER NP molar ratio on the barrier function and lipid organization. Show less
The stratum corneum (SC), the thin uppermost layer of the skin, consists of dead flattened skin cells (corneocytes) embedded in a lipid matrix. The lipid matrix is considered to play a crucial role... Show moreThe stratum corneum (SC), the thin uppermost layer of the skin, consists of dead flattened skin cells (corneocytes) embedded in a lipid matrix. The lipid matrix is considered to play a crucial role in the skin barrier function. It consists of ceramides (CER), cholesterol (CHOL) and free fatty acids (FFA) forming crystalline lipid lamellae. From studies with native SC and SC lipid models much information has been gained on the phase behavior of the SC lipid matrix. However, little is known about the correlation between SC lipid organization and the permeability of the SC. This is difficult to investigate using native SC, due to its complex structure. Therefore SC lipids were casted on a porous membrane, resulting in a lipid organization and lamellar orientation similar to that in SC. This lipid membrane is referred to as the stratum corneum substitute (SCS). The SCS can be used to perform diffusion studies. Therefore, when modifying the lipid composition and thus the lipid organization in the SCS, it is possible to study the relationship between lipid organization and permeability. The main objectives of this thesis are 1) to investigate the influence of lipid organization on the barrier function in the SCS and 2) to obtain insights in the molecular organization within the unit cell of the lamellar phases in SC. Show less
