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 referred ...

and compose most of the

stratum corneum The stratum corneum (Latin for 'horny layer') is the outermost layer of the epidermis. The human stratum corneum comprises several levels of flattened corneocytes that are divided into two layers: the ''stratum disjunctum'' and ''stratum compact ...

, 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 hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...

. They are regularly replaced through

desquamation Desquamation occurs when the outermost layer of a tissue, such as the skin, is shed. The term is . Physiologic desquamation Keratinocytes are the predominant cells of the epidermis, the outermost layer of the skin. Living keratinocytes reside in ...

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 cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

barrier.

Structure

Corneocytes are

without nuclei and

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

organelles In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...

. They contain a highly insoluble cornified envelope within the

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

, and

lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

(

fatty acid In chemistry, particularly 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, fr ...

sterol Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the go ...

s and

ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetylsphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up ...

s) released from

lamellar bodies In cell biology, lamellar bodies (otherwise known as lamellar granules, membrane-coating granules (MCGs), keratinosomes or Odland bodies) are secretory organelles found in type II alveolar cells in the lungs, and in keratinocytes in the skin. The ...

within the

. The corneocytes are interlocked with each other and organized as vertical columns of 10–30 cells to form the

. 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

. 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,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...

. 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 The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar or ...

of the epidermis will multiply through

cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...

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

differentiation. Corneocytes, also referred to as squames (from

Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...

''squama'', meaning a “thin flake” or “scales”) are terminally differentiated, anucleated cells of

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 (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than ...

(UV) irradiation. Major constituents of corneocytes are

keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ho ...

intermediate filaments Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma''. Intermedia ...

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 grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

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 held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...

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 α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...

-rich proteins called

filaggrin Filaggrin (filament aggregating protein) is a filament-associated protein that binds to keratin fibers in epithelial cells. Ten to twelve filaggrin units are post-translationally hydrolyzed from a large profilaggrin precursor protein during termina ...

, which are responsible for aggregating

filaments to form

bundles that maintain the rigid structure of the cells in stratum corneum. When

is degraded,

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important r ...

, pyrrolidone carboxylic acid (1,2),

glutamic acid Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...

and other

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

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 In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

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

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 cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...

in the upper part of stratum spinosum. From the site of production, lamellar bodies migrate to the top of the

stratum granulosum The stratum granulosum (or granular layer) is a thin layer of cells in the epidermis lying above the stratum spinosum and below the stratum corneum (stratum lucidum on the soles and palms).James, William; Berger, Timothy; Elston, Dirk (2005) ''A ...

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 contribute to permeability barrier

homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...

of the stratum corneum. The homeostasis function is regulated by the

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

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

levels in the stratum corneum but decreases it in the stratum granulosum. This perturbation induces lamellar bodies to undergo

exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...

and secrete lipids such as glycosylceramides,

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

and

phospholipids Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

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 Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetylsphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up ...

(30-50% by mass),

(25% by mass) and free

fatty acids In chemistry, particularly 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, f ...

(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 medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon di ...

Cornified envelope

The cornified envelope is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

shell that surrounds each corneocyte. Its thickness varies between 15 and 20 nm. The highly

insoluble 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 solubil ...

cornified envelope is formed by

cross-link In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...

ing of soluble precursor proteins such as

loricrin Loricrin is a protein that in humans is encoded by the ''LOR'' gene. Function Loricrin is a major protein component of the stratum corneum, cornified cell envelope found in terminally differentiated epidermis (skin), epidermal cells. Loricrin ...

involucrin Involucrin is a protein component of human skin and in humans is encoded by the ''IVL'' gene. In binding the protein loricrin, involucrin contributes to the formation of a cell envelope that protects corneocytes in the skin. Gene This gene i ...

envoplakin Envoplakin is a protein that in humans is encoded by the ''EVPL'' gene. Interactions Envoplakin has been shown to interact Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c) ...

and

periplakin Periplakin is a protein that in humans is encoded by the ''PPL'' gene. The protein encoded by this gene is a component of desmosomes and of the epidermal cornified envelope in keratinocytes. The N-terminal domain of this protein interacts with th ...

Corneodesmosomes and desquamation

The overall integrity of the stratum corneum is maintained by specialized intercellular proteins called corneodesmosomes. Three adhesive proteins

desmoglein-1 Desmoglein-1 is a protein that in humans is encoded by the ''DSG1'' gene. Desmoglein-1 is expressed everywhere in the skin epidermis, but mainly it is expressed in the superficial upper layers of the skin epidermis. Function Desmosomes are cell ...

, desmocollin-1 and

corneodesmosin Corneodesmosin is a protein that in humans is encoded by the ''CDSN'' gene. This gene encodes a protein found in corneodesmosomes, which localize to the human epidermis and other cornified squamous epithelia. During maturation of the cornified lay ...

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 In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

from colonizing the skin, and is referred to as

. 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 Xeroderma, xerosis or xerosis cutis, or simply dry skin, is a skin condition characterized by excessively dry skin. The medical term ''xeroderma'', meaning "dry skin", derives from modern Latin, ''xero-'' 'dry' + Greek ''derma'' 'skin'. In most ...

) 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 Patholo ...

), 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

and

elastin Elastin is a protein that in humans is encoded by the ''ELN'' gene. Elastin is a key component of the extracellular matrix in gnathostomes (jawed vertebrates). It is highly elastic and present in connective tissue allowing many tissues in the bod ...

Localization

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

References

{{Reflist