Generality
The real defensive barrier against dehydration is located in the stratum corneum, ie in the most superficial portion of the epidermis. This barrier serves not only to regulate the loss of water from the body, but also to modulate the percutaneous absorption of the various substances applied to the skin.
The barrier function exerted by the stratum corneum is mainly due to its typical "cemented wall" structure, in which the bricks are constituted by the corneocytes and their covering, while the cement consists of lipid substances.
This structure will be analyzed in detail below.
Horny layer
The stratum corneum is formed by two compartments: one cellular (the corneocytes, then the bricks) and one extracellular (the cement), rich in lipids that fill the spaces existing between one cell and another.
The corneocytes are extremely flattened cells, with no nucleus and a large surface (on average one square millimeter). Their extension tends to increase considerably with age. This happens because - with the progress of time - the desquamation and the consequent replacement of the epidermis occur more slowly, allowing the corneocytes to remain in the superficial layers for a long time.
The corneocytes constitute the final stage of the complex process of differentiation of keratinocytes that originate from the deeper layers of the epidermis.
As mentioned, the cells resulting from this differentiation are anucleate cells (that is, devoid of nucleus) whose cytoplasm does not contain organelles, but consists for the most part (more than 80%) of keratin filaments aggregated in macrofibrils which, at in turn, they are joined together thanks to the presence of a protein matrix consisting of filaggrin.
Horny coating
The corneocytes are surrounded by a corneous lining: a proteic shell whose task is to confer a certain resistance to mechanical traumas and chemical insults.
The corneous lining is a specialized structure that replaces the cell membrane. During the process of keratinocyte differentiation, in fact, the latter is gradually replaced by the subsequent apposition of a series of proteins: involucrin, loricrine, keratolinin (or cystatin) and SPRRs ( Small Proline-Rich Proteins, a family comprising at least 15 different types of proteins).
In detail, loricrina fixes the keratin macrofibrils present in the corneocytes with the external horny coating, thus giving a certain resistance to the skin surface.
Given the nature and characteristics of the horny coating, it is also known as the "protein envelope".
Intercorneocyte cement
Intercorneocyte cement (or lipid cement) is the material that holds the bricks together (corneocytes) that make up the typical wall structure of the stratum corneum.
The task of the intercorneocyte cement, therefore, is to keep the corneocytes firm to each other, sealing the spaces between the cells and thus guaranteeing the impermeability of the structure.
As previously mentioned, this cement is made up of lipid substances (intercellular lipids) and its synthesis occurs during the processes of keratinocyte differentiation.
The intercellular lipids, in fact, come from the lamellar bodies of Odland (or keratinosomes), organelles present in the granular layer of the epidermis. They are vesicles provided with a membrane which contain numerous lamellar layers of lipids (hence the name lamellar bodies), arranged one above the other, a bit like a stack of plates.
The content of these vesicles is rich and varied and includes:
- Fatty substances such as phospholipids, glucosyl-ceramides, cholesterol and sphingomyelin which form the aforementioned lamellar lipids;
- Non-enzymatic proteins;
- Enzymes;
- Molecules with antimicrobial activity.
However, during keratinocyte differentiation, the membrane of Odland's lamellar bodies fuses with the membrane of the highest cells of the granular layer and the lipids are emitted to the outside by exocytosis. These fats are then placed between one corneocyte and another, forming long laminae: each of them is organized in a bilayer layer, a bit like the phospholipid double layer that characterizes the cell membrane. These layers are stratified, giving rise to what is commonly referred to as "multilamellar fat".
The fatty substances contained in Odland's bodies - despite being lipophilic - are not completely apolar. This characteristic is lost when they are extruded from the vesicle: the glucosyl-ceramides become ceramides, the cholesterol is largely esterified and the phospholipids are hydrolysed by the enzyme phospholipase A2, with consequent release of free fatty acids.
The final result is a completely hydrophobic lipid complex, that is impermeable to water.
Moreover, it is good to remember that the free fatty acids deriving from the aforementioned hydrolysis reaction, are essential not only for the performance of the barrier function, but also for maintaining the acid pH at the level of the stratum corneum.
The ceramides, on the other hand, are placed at the interface between the lipidic cement itself and the horny coating that replaces the cell membrane in the corneocytes.
corneodesmosomes
The integrity of the stratum corneum is also guaranteed by the presence of numerous corneodesmosomes that act as points of attachment between the various corneocytes, both between those of the same row and between those of the upper and lower layers.
However, in the more superficial portions, the integrity of the stratum corneum is smaller due to the desquamation processes that are regulated at the physiological level.
For the desquamation of the corneocytes to occur, the proteins that make up the corneodesmosomes must be hydrolyzed by specific proteases. The stratum corneum is therefore the site of a discrete enzymatic activity.
Water Content of the Horny Layer
In order for the skin barrier represented by the stratum corneum to be efficient, it is necessary that the water content of this region remains constant.
The corneocytes are poor in water; to make a comparison in the stratum corneum the water represents only 15% of the cellular weight, while in the underlying epidermis this percentage reaches 70%.
As mentioned a few lines ago, the water content of the corneocytes, although low, must absolutely remain constant. This aspect is fundamental both for maintaining cellular flexibility and for maintaining enzymatic activity (such as the aforementioned proteases that must degrade corneodesmosomes to allow skin desquamation).
The water content of the corneocytes is influenced by the ambient temperature and the degree of humidity. If the external environment is very dry these cells tend to dehydrate, on the contrary, if immersed in water, they absorb it up to 5-6 times their weight. This, together with the absence of sebum, explains why, after a prolonged soak, the skin of the fingertips tends to wrinkle. In these cases the cells of the stratum corneum absorb water and tend to increase in volume. Given the reduced size of the skin in these areas, the corneocytes swell but fail to expand and thus form the characteristic wrinkles.
In any case, the water cannot penetrate in high quantities below the stratum corneum, due to the presence of the intercellular lipids that constitute the intercorneocyte cement.
Natural Hydration Factor
The natural hydration factor - also called NMF (from the English Natural Moisturizing Factor ) - is a mixture of various water-soluble and highly hygroscopic substances (able, that is, to absorb a lot of water) present both inside the corneocytes and in the spaces intercorneocitari. It is important to maintain hydration of the stratum corneum as a whole.
In detail, the NMF is composed of:
- Free amino acids;
- Organic acids and their salts;
- Nitrogen compounds (such as, for example, urea);
- Inorganic acids and their salts;
- Saccharides.
Amino acids are the main substances that make up the natural hydration factor. Many of them are supplied by filaggrin, the protein that supports keratin filaments inside the corneocytes and is subsequently degraded.
As mentioned, the natural moisturizing factor is abundantly present inside the corneocytes, where it performs humectant functions (that is, it guarantees the hydration of the stratum corneum retaining that 15% of water that we have seen to be very important for the health of the skin).
