Collagen

Collagen is the main structural protein in the extracellular matrix of the connective tissue of many animals. It is the most abundant protein in mammals, making up 25–35% of total protein content. Its amino acids form a triple helix in long fibrous structures found mainly in cartilage, bone, tendon, ligament, and skin. Vitamin C is essential for its synthesis. Collagen provides the high tensile strength that supports the structure of tissues, whereas the elasticity and recoil by which skin returns to its original shape after being stretched are provided mainly by elastin.

The name collagen derives from the Greek word κόλλα (kólla), meaning "glue", and the suffix -gen, meaning "producing". It was first used in English in 1843.

Structure and function

Composition

A collagen molecule is a triple helix formed by three twisted polypeptide chains (alpha chains), typically two identical α1 chains and one α2 chain of slightly different composition. Its amino acid composition differs from that of most proteins in its high content of hydroxyproline. The most common repeating motifs in the sequence are glycine–proline–X and glycine–X–hydroxyproline; glycine occupies nearly every third residue, and proline accounts for about 17%. Because glycine, the amino acid with the smallest side chain, sits at the center of the helix, the triple helix can form stably only when glycine occupies that position.

As of 2011, 28 types of collagen had been reported in humans, each containing at least one triple helix. More than 90% of human collagen is type I or type III. The five most common types are as follows.

• Type I: skin, tendon, blood vessels, organs, and bone (the main component of the organic part of bone)
• Type II: the main collagen component of cartilage
• Type III: the main component of reticular fibers, commonly found together with type I
• Type IV: forms the basal lamina of the basement membrane
• Type V: found in skin (especially around hair follicles and sweat glands) and in the placenta; studied for its roles in wound healing and in connecting the dermis and epidermis

Distribution in tissues

Besides cartilage, bone, tendon, ligament, and skin, collagen is abundant in the cornea, blood vessels, the gut, intervertebral discs, and dentin, and in muscle it is a major component of the endomysium. The cells that most commonly produce collagen are fibroblasts.

In the dermis of the skin, collagen is the basic material forming the dermal structure, and collagen fibers are reported to account for about 90% of all dermal fibers. Type I collagen predominates in skin, and collagen is produced not only by fibroblasts but also by endothelial and epithelial cells. At the dermal–epidermal junction, type VII collagen forms anchoring fibrils.

Properties

Tensile strength

Collagen is a long, tough fibrous structural protein with great tensile strength, and it is the main component of fascia, cartilage, ligaments, tendons, bone, and skin. In tendon the fibers are arranged mostly in parallel, whereas in skin wavy fibers form a network; as a result, tendon has much higher strength and lower ductility than skin.

Differences between collagen and elastin

Collagen and elastin are both major extracellular matrix fibers of the dermis, but they play different roles in skin. Collagen forms the dermal structure and provides tensile strength, while elastin provides the elasticity and recoil that return skin deformed by an external force to its original shape.

Comparison of collagen and elastin

Item	Collagen	Elastin
Main role in skin	Forms the dermal structure and provides tensile strength	Provides the elasticity and recoil that return deformed skin to its original shape
Molecular structure	Triple helices assemble into fibrils and fibers	An insoluble, amorphous protein that makes up about 90% of the elastic fiber, surrounded by a layer of microfibrils
Main amino acids	Glycine (nearly every third residue), proline, hydroxyproline	Glycine, valine, alanine, proline
Cross-linking	Depends on lysyl oxidase and copper	Depends on lysyl oxidase and copper; desmosine and isodesmosine cross-links give elasticity
Amount in skin	About 90% of dermal fibers	Elastic fibers account for about 4% of the dry weight of the dermis
Synthesis	Also produced by endothelial and epithelial cells, not only fibroblasts	Synthesis is concentrated around the neonatal period and is rare in adult fibroblasts; half-life of 70 years or more
Changes with aging	Total amount decreases and fibers are fragmented by enzymes; reduced dermal collagen content lowers dermal thickness	In intrinsic aging the number and size of fibers decrease; in photoaging, nonfunctional elastotic material accumulates

The position of elastin in skin elasticity

Noh (2021) explained that the decrease in skin thickness with aging is not as large as might be expected, that the loss of elasticity far exceeds the loss of thickness, and that changes in elastic fibers contribute greatly to this functional loss. The same article noted that, because the main function of elastic fibers is to return deformed skin to its original shape, it is unreasonable to present increased collagen production or inhibited collagen degradation alone as evidence of improved skin elasticity. Kim et al. (2022) likewise described elastin as a highly elastic ECM fiber that gives tissue the ability to recover after deformation, and held that because skin aging begins with the loss of elasticity, skin aging care should start with elasticity care. However, English Wikipedia states that collagen, together with elastin and soft keratin, is responsible for the strength and elasticity of skin, and that the degradation of collagen leads to wrinkles that accompany aging.

Biosynthesis

Collagen synthesis occurs both inside and outside the cell. The formation of fibrillar collagen proceeds as follows.

1. Gene transcription: About 45 genes (whose names usually begin with COL) are involved in forming collagen, and they encode the 28 types of collagen. Type I, which is abundant in skin, is made from α1 and α2 chains.
2. Formation of the precursor peptide: The mRNA is translated and enters the endoplasmic reticulum as preprocollagen.
3. Formation of procollagen: The signal peptide is removed, and hydroxyl groups are added to proline and lysine to form hydroxyproline and hydroxylysine. The enzymes for this reaction require vitamin C as a cofactor; a prolonged lack of vitamin C impairs collagen synthesis and causes scurvy. Glycosylation follows, and the three chains form a triple helix.
4. Modification and secretion: Procollagen undergoes final modification in the Golgi apparatus and is packaged into secretory vesicles for release from the cell.
5. Formation of tropocollagen: Outside the cell, enzymes remove the propeptides at both ends of procollagen to form tropocollagen. Defects at this step cause collagen disorders such as some forms of Ehlers–Danlos syndrome.
6. Formation of collagen fibers: Lysyl oxidase, a copper-dependent enzyme, creates aldehyde groups on lysine and hydroxylysine, which form covalent bonds between tropocollagen molecules to produce collagen fibrils. Fibrils assemble into collagen fibers.

Collagen fibers can attach to the cell membrane through proteins such as fibronectin, laminin, fibulin, and integrin. Cortisol stimulates the breakdown of skin collagen into amino acids. Cross-linking by lysyl oxidase and copper is also a key step in the biosynthesis of elastin.

Research

Skin aging and collagen

In the dermis, the total amount of collagen decreases with aging and the fibers are fragmented by various enzymes. A reduction in the amount and function of collagen is described as impairing fibroblast function and further reducing dermal collagen. Noh (2021) considered the importance of increased collagen for improving wrinkles to be clear, but held that changes in elastic fibers and elastin also contribute greatly to skin aging.

In vitro study

Chung et al. (2021) treated human dermal fibroblasts (Hs27) with amino acid mixtures and copper and compared the expression of collagen I (COL1A2) and elastin (ELN). Certain formulations containing copper (EL4 and EL11) significantly increased the expression of both genes and of collagen I and elastin proteins. Amino acids alone had no effect; copper alone also increased gene and protein expression, but the increase in protein was larger when amino acids were added.

Supplements and cosmetics

English Wikipedia states that collagen dietary supplements are marketed for improving skin elasticity and reducing wrinkles, but that there is no good evidence that ingesting them affects collagen production or skin health. Ingested collagen is digested into hydrolyzed peptides and amino acids, so intact collagen does not enter damaged skin, and topical cosmetics containing collagen have low permeability and are not absorbed by the skin. As of 2025, there is reportedly no clinical evidence that oral or topical collagen improves wrinkles or skin aging. Noh (2021) also noted that, although studies have reported increased skin elasticity after oral intake of certain amino acids, verification is still insufficient.

Medical applications

Collagen is used as a medical biomaterial in artificial skin, burn and wound dressings, scaffolds for tissue regeneration, and bone and dental regeneration.

Related diseases

Collagen-related diseases arise mainly from genetic defects or nutritional deficiencies that affect collagen biosynthesis, assembly, post-translational modification, or secretion. About 1,000 mutations have been identified in 12 types of collagen; representative disorders include osteogenesis imperfecta and Ehlers–Danlos syndrome.

Limitations

The human trial by Kim et al. (2022) was a small, uncontrolled study of five subjects, and its authors stated that studies directly measuring changes in collagen and elastin content in tissue are needed.