Corneocytes are terminally differentiated

keratinocytes Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes refer ...

and compose most of the stratum corneum, the outermost layer of the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

. They are regularly replaced through desquamation and renewal from lower epidermal layers and are essential for its function as a

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

barrier.

Structure

Corneocytes are

without nuclei and

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

ic organelles. They contain a highly insoluble cornified envelope within the plasma membrane, and

lipids Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...

(

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

sterol A sterol is any organic compound with a Skeletal formula, skeleton closely related to Cholestanol, cholestan-3-ol. The simplest sterol is gonan-3-ol, which has a formula of , and is derived from that of gonane by replacement of a hydrogen atom on ...

s and

ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of Eukaryote, eukaryotic cells, since they are co ...

s) released from lamellar bodies within the

. The corneocytes are interlocked with each other and organized as vertical columns of 10–30 cells to form the stratum corneum. Corneocytes in the lower part of the stratum corneum are bridged together through specialized junctions ( corneodesmosomes). Those junctions disintegrate as corneocytes migrate toward the surface of the skin and result in desquamation. At the same time, as those loosened junctions encounter more hydration, they will expand and connect together, forming potential entry pores for

microorganisms A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...

. The stratum corneum can absorb three times its weight in water, but if its water content drops below 10%, it no longer remains pliable and cracks.

Formation

Corneocytes are

in their last stage of differentiation. Keratinocytes in the stratum basale of the epidermis will multiply through cell division and migrate toward the

surface. During that migration keratinocytes will undergo multiple stages of differentiation to finally become corneocytes once they reach the stratum corneum. As corneocytes are continually eliminated through desquamation or through rubbing, skin washing or detergents they are also continually formed through keratinocyte differentiation. Corneocytes, also referred to as squames (from

Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...

''squama'', meaning a "thin flake" or "scales") are terminally differentiated, anucleated cells of keratinocyte lineage that constitute the majority of stratum corneum, the outermost layer of the epidermis. Size of a corneocyte is approximately 30-50 μm in diameter and 1 μm thick, and the average area of corneocytes at the surface of the skin reaches approximately 1000 μm², but may vary according to anatomical location, age and external environmental conditions such as

ultraviolet Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of ...

(UV) irradiation. Major constituents of corneocytes are keratin intermediate filaments organized in parallel bundles to form a matrix to give rigidity to the overall structure of the skin.

Functions

Layers of corneocytes produce high mechanical strength which allows epidermis of the skin to perform its function as a physical, chemical and immunological barrier. For example, corneocytes act as UV barrier by reflecting the scattered UV radiation, protecting cells inside the body from

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

and DNA damage. As corneocytes are essentially dead cells, they are not prone to viral attacks, though invisible microabrasions may cause permeability. Colonization of pathogens in the skin is prevented via complete turnovers of corneocyte layer every 2–4 weeks. Corneocytes are also capable of absorbing and storing small amounts of water to keep the skin hydrated and maintain its flexibility.

Intracellular structures

Natural moisturizing factor

Corneocytes contain small

molecules A molecule is a group of two or more atoms that are held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemistry ...

called natural moisturizing factors, which absorb small amounts of water into the corneocytes thereby hydrating the skin. The natural moisturizing factor is a collection of

water-soluble In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solub ...

compounds produced from the degradation of

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...

-rich proteins called filaggrin, which are responsible for aggregating keratin filaments to form keratin bundles that maintain the rigid structure of the cells in stratum corneum. When filaggrin is degraded,

urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...

, pyrrolidone carboxylic acid (1,2), glutamic acid and other

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

are produced. These are collectively referred to as the ''natural moisturizing factor'' of the skin. The components of the natural moisturizing factor absorb water from the atmosphere to ensure that the superficial layers of the stratum corneum stay hydrated. As they are

themselves, excessive water contact may leach them and inhibit their normal functions which is why prolonged contact with water makes the skin drier. The intercellular lipid layer helps prevent the loss of natural moisturizing factor by sealing the outside of each corneocyte.

Extracellular structures

Although stratum corneum is mostly composed of corneocytes, other supporting structures are present in the extracellular matrix to assist in the function of stratum corneum. These include: *Lamellar bodies *Intercellular lipids (lamellar lipid bilayer) *Cornified envelope *Corneodesmosomes

Lamellar bodies

Lamellar bodies are tubular or ovoid-shaped secretory organelles derived from the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

in the upper part of stratum spinosum. From the site of production, lamellar bodies migrate to the top of the stratum granulosum and then into the intercellular domain of the stratum corneum to extrude their contents, which are predominantly

. The

ultimately form the lamellar lipid bilayer that surrounds corneocytes and also contributes to the permeability barrier

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

of the stratum corneum. The homeostasis function is regulated by the calcium gradient in the epidermis. Usually the calcium level is very low in stratum corneum, but high in stratum granulosum. Once the permeability barrier is disrupted an influx of water occurs in the stratum corneum, which in turn increases the calcium levels in the stratum corneum but decreases it in the stratum granulosum. This perturbation induces lamellar bodies to undergo exocytosis and secrete lipids such as glycosylceramides,

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

and phospholipids to retrieve the permeability barrier function of stratum corneum.

Intercellular lipids (lamellar lipid bilayer)

Corneocytes are embedded in a matrix of specialized lipids that constitute approximately 20% of the stratum corneum volume. The major constituents of the intercellular lipids in stratum corneum include ceramides (30-50% by mass),

(25% by mass) and free

fatty acids In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

(10-20% by mass), mostly produced by lamellar bodies. These hydrophobic components fuse together to form multiple bilayers of lipids between corneocytes to act as the principal barrier to the transcutaneous movement of water and

electrolytes An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble salts, acids, and bases, dissolved in a polar solvent like water. Upon dissolving, t ...

Cornified envelope

The cornified envelope is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

shell that surrounds each corneocyte. Its thickness varies between 15 and 20 nm. The highly insoluble cornified envelope is formed by cross-linking of soluble precursor proteins such as loricrin, involucrin, envoplakin and periplakin.

Corneodesmosomes and desquamation

The overall integrity of the stratum corneum is maintained by specialized intercellular proteins called corneodesmosomes. Three adhesive proteins desmoglein-1, desmocollin-1 and corneodesmosin compose the corneodesmosomes and provide the cohesive forces to connect the adjacent corneocytes. The components of the corneodesmosomes are gradually degraded by the enzymes that digest proteins, as the corneocytes are pushed towards the surface of the skin. As a result of the weakened corneodesmosomes in the outer skin surface, the uppermost layers of corneocytes get exfoliated through frictional forces such as rubbing or washing. This process is a normal protective mechanism of the skin to prevent pathogens from colonizing the skin, and is referred to as desquamation. In healthy skin, desquamation is an invisible process and the stratum corneum is turned over completely within 2–4 weeks, while maintaining the tissue thickness.

Pathologies

Dry skin (xerosis)

Dry skin ( xerosis) involves increased thickness of stratum corneum (

hyperkeratosis Hyperkeratosis is thickening of the stratum corneum (the outermost layer of the epidermis, or skin), often associated with the presence of an abnormal quantity of keratin,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathol ...

), which may occur due to various reasons including aging, humidity of the environment or UV irradiation. The accumulation of corneocyte clumps on the surface of the skin may lead to abnormal detachment of squames as visible clusters. Xerosis is common, especially in elderly individuals which may be due to decreased quantity of free

, a constituent of natural moisturizing factor. Consequently, many moisturizers in the markets incorporate the components of the natural moisturizing factor as well as keratin and

elastin Elastin is a protein encoded by the ''ELN'' gene in humans and several other animals. Elastin is a key component in the extracellular matrix of gnathostomes (jawed vertebrates). It is highly Elasticity (physics), elastic and present in connective ...

Localization

Corneocytes are part of the stratum corneum of the epidermis and contribute to the barrier function of the skin.

References

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