CORNEOCYTES: GENERAL CHARACTERISTICS, HISTOLOGY, FUNCTIONS - ANATOMY AND PHYSIOLOGY - 2025

The corneocytes or keratinocytes enucleated are squamous cell, flattened and coreless form the essential element of the skin barrier being more differentiated epidermal cells.

The corneocytes together make up the stratum corneum "stratum corneum", a metabolically inactive or dead layer of the epidermis. All epidermal strata make up the characteristic keratinized flat epithelium of the skin.

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The horny cells of the epidermis represent the last phase of keratinization from the basement or germ membrane (keratinocyte). These cells have a strong corneal envelope and a very reduced, fibrillar cytoplasm, full of keratin and without the presence of cellular organelles.

General characteristics

The skin, structurally speaking, is an effective barrier between the outside and the inside of the body. In this way, an "internal" barrier is created to prevent evaporation and an "external" one against the mechanical, chemical and microbial effects of the environment.

The main objective of the epidermis differentiation process in mammals is to generate a relatively impermeable horny outer layer. This process is considered a specialized form of apoptosis whose end product is an almost completely keratinized cell.

In order to fulfill these functions, a process of keratinization or cellular maturation occurs from the cells present in the proliferative (basal) layer with great mitotic potential to the superficial scales of the corneal layer.

Corneocytes are quite differentiated keratinocytes due to the cornification process. During this process, the objective is to form a resistant, waterproof and constantly renewing membrane. The arrangement of corneocytes in the squamous stratum is also known as "in bricks and mortar".

These squamous cells are renewed quickly, involving a complete replacement of the stratum corneum in a time range that goes from approximately 15 to 30 days in a skin without problems.

Keratinization processes

In general, the epidermal basal cell begins to synthesize intermediate keratin filaments that concentrate and form tonofibrils. This cell then enters the spinous stratum, where the synthesis of intermediate keratin filaments continues.

In the superficial part of this layer, the production of keratohyalin granules begins. These contain proteins such as filaggrin and trichohyalin associated with intermediate filaments, in addition to lamellar bodies with glycolipids.

Already in the stratum granulosa, the cell expels laminar bodies that contribute to the formation of a water barrier in the stratum corneum.

The remainder of the cytoplasm of the granular keratinocyte contains abundant keratohyalin granules that are deeply associated with tonofilaments, forming the cell envelope. The existence of these granules is evidence of cellular keratinization.

An increase in the concentration of calcium in the granular stratum causes the release of the content of the keratohyalin granules. In this way, the profilaggrin that is converted into active filaggrin monomers, binds to the intermediate keratin filaments, aggregating and compacting them, which causes the collapse of the cell to its flat form.

The process of migration of the cell from the stratum granulosa to the stratum corneum takes approximately 6 hours.

Corneocyte formation

The transformation of the granular cell to cornified includes the destruction of the nucleus and all the cellular organelles, as well as a significant thickening of the membrane and a decrease in pH in this stratum.

The cells of the stratum corneum are depleted of lipids and in turn are embedded in an interstitium rich in neutral lipids, constituting an effective barrier against water. The neutral lipids function as a cement arranged in laminar bilayers between the corneocytes and come from the lamellar bodies released in the granular layer.

The corneocytes are strongly linked to each other through corneodesmosomes and are covered by a cornified cell envelope, which has a protein portion produced by the production of structural proteins (up to 85%) and another lipid portion, which provides mechanical and chemical resistance..

Although the role of so many lipids is not exactly known, it is believed that they participate in the modulation of the permeability of the skin. They also represent a link for the organization of corneocyte cohesion and desquamation of the stratum corneum.

During the cornification process, a large fraction of lipids (such as sphingolipids) disappear and are replaced by the accumulation of free and esterified sterols.

Corneocyte desquamation

The desquamation or superficial exfoliation of the squamous layer is a basically proteolytic process that is regulated. The latter consists of the degradation of the corneodesmosomes of the corneal cells, which occurs from the action of serine peptidases related to kallikrein such as KLK5, KLK7 and KLK14.

As the pH decreases as a consequence of the degradation of filaggrin by different proteases and the release of amino acids in the superficial layers of the epidermis, these proteins (KLKs) are released that degrade the desmosomes between cells, allowing the exfoliation of the cells. themselves. This allows a controlled renewal of the skin from the existing pH gradient.

Histology

The stratum corneum is made up of multiple layers of corneocytes, which have a variable thickness depending on the anatomical region of between 10-50 µm. The thickness tends to be minimum in the mucosal regions (thin skin) and maximum in the soles, palms of the feet and hands, elbows and knees (thick skin).

Corneocytes are made up of 40% proteins, 20% lipids and water (approximately 40%). The corneocyte cell envelope contains 15 nm of insoluble proteins such as cystaine, desmosomal proteins, filaggrin, involucrin or 5 different keratin chains, among others.

The lipid envelope is made up of a 5nm layer of lipids linked by ester type bonds, the main components being sphingolipids (ceramides), cholesterol and free fatty acids, being acylglucosylceramide molecules of great importance.

The stratum corneum presents small alterations around the hair follicles, where only the upper part of the follicular apparatus (acroinfundibulum) is protected by a coherent stratum corneum. On the other hand, in the lower part (infrainfundibulum) the corneocytes appear to be undifferentiated and protection is incomplete or absent.

For this reason, these regions constitute a pharmacological target for the skin, since even solid particles can enter through the follicular route.

Features

The main physical barrier between the external environment and the internal environment is basically the stratum corneum. Together with the internal layers, they protect the body from various factors, participating in the maintenance of body homeostasis.

The stratum corneum represents the physical barrier itself, while the subsequent layers (epidermis with nucleated cells) constitute the chemical barriers. Specifically, it prevents the entry of harmful substances, the loss of fluids and the excessive accumulation of bacteria on the skin surface.

In addition, they have a strong cornified cytoplasmic membrane coated on the outside by various lipid compounds that form the main component to repel water. The latter is determined by the deposition of insoluble proteins on the inner surface of the membrane and a layer of lipids that consolidate on the outer surface.

Stratum corneum and topical treatments

The stratum corneum is also a highly efficient barrier to drug entry. In some dermatological treatments, the entry paths of these topics can be through several routes, one of them being the entry through the corneocytes (transcellular route), which will depend on the size of the corneocytes and is the most important route.

The larger the corneocytes, the lower the diffusion coefficient. However, bearing in mind that the stratum corneum is lipophilic, fat-soluble drugs have greater ease of crossing it.

On the other hand, drugs can enter through the intercornocyte spaces that only represent 5% of the volume of the corneal layer, so their participation in absorption is minimal. And a third way is through the skin appendages whose absorption is even lower.

References

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