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 made up of corneocytes and their coating, while the cement is made up of lipid substances.
This structure will be analyzed in detail below.
Horny layer
The stratum corneum is formed by two compartments: a cellular one (the corneocytes, therefore the bricks) and an extracellular one (the cement), rich in lipids that fill the spaces existing between one cell and the other.
Corneocytes are extremely flattened cells with no nucleus and with a large surface area (on average one square millimeter). Their extent tends to increase considerably with advancing 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 the keratinocytes that originate from the deeper layers of the epidermis.
As mentioned, the cells resulting from this differentiation are anucleated (i.e., nucleus-less) cells whose cytoplasm does not contain organelles, but is made up for the most part (more than 80%) of keratin filaments aggregated in macrofibrils which, at in turn, they are joined to each other thanks to the presence of a protein matrix consisting of filaggrin.
Horny Coating
The corneocytes are surrounded by a horny covering: a protein envelope whose task is to confer a certain resistance to mechanical trauma and chemical insults.
The horny lining is a specialized structure that replaces the cell membrane. During the keratinocyte differentiation process, in fact, the latter is gradually replaced by the subsequent addition of a series of proteins: involucrin, loricrin, keratolinin (or cystatin) and SPRRs (Small Proline-Rich Proteins, a family comprising at least 15 different types of proteins).
In detail, loricrin fixes the keratin macrofibrils present inside the corneocytes with the external horny lining, thus conferring 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
The intercorneocyte cement (or lipid cement) represents the material that holds together the bricks (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 differentiation processes of the keratinocytes.
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 membrane that contain numerous lamellar layers of lipids (hence the name lamellar bodies), arranged one on top of 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.
In any case, during the differentiation of the keratinocytes, the membrane of the lamellar bodies of Odland merges 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 arranged between a corneocyte and the other, forming long laminae: each of them is organized in a bilayer layer, a bit like the phospholipid bilayer that characterizes the cell membrane. These laminae stratify, giving rise to what is commonly defined as "multilamellar fat ".
The fatty substances contained in Odland's bodies - despite being lipophilic - are not entirely 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 hydrolyzed by the enzyme phospholipase A2, with consequent release of free fatty acids.
The final result is a completely hydrophobic lipid complex, ie impermeable to water.
Furthermore, it should be remembered that the free fatty acids deriving from the aforementioned hydrolysis reaction are essential not only for carrying out the barrier function, but also for maintaining the acid pH at the level of the stratum corneum.
The ceramides, on the other hand, are arranged at the interface between the same lipid cement and the corneous lining that replaces the cell membrane in the corneocytes.
Corneodesmosomes
The integrity of the stratum corneum is also guaranteed by the presence of numerous corneodesmosomes which 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 lower due to the desquamation processes which are regulated at the physiological level.
In order for corneocyte desquamation to occur, the proteins that make up the corneodesmosomes must be hydrolyzed by specific proteases. The stratum corneum is therefore the site of a moderate enzymatic activity.
Water content of the stratum corneum
For the skin barrier represented by the stratum corneum to be efficient, the water content of this region must remain constant.
Corneocytes are poor in water; to make a comparison, in the stratum corneum, water represents only 15% of the cell 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 which must degrade the 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 own weight. This, together with the absence of sebum, explains why, after a soak prolonged, 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 extension of the skin in these areas, the corneocytes swell but are unable to expand and thus form the characteristic wrinkles.
In any case, the water is unable to penetrate in large quantities below the stratum corneum, due to the presence of intercellular lipids that make up the inter-corneocyte 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 (that is, capable of absorbing a lot of water) present both inside the corneocytes and in the inter-corneocyte spaces. It is important for maintaining the 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 the keratin filaments inside the corneocytes and which is subsequently degraded.
As mentioned, the natural hydration factor is abundantly present inside the corneocytes, where it performs humectant functions (that is, it guarantees the hydration of the stratum corneum by retaining that 15% of water that we have seen to be very important for the health of the skin).
