Collagen () is the main structural in the found in the body's various s. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole-body protein content. Collagen consists of s bound together to form a of elongated known as a . It is mostly found in such as , s, s, s, and . Depending upon the degree of , collagen tissues may be rigid (bone) or compliant (tendon) or have a gradient from rigid to compliant (cartilage). Collagen is also abundant in s, s, the , s, and the in teeth. In , it serves as a major component of the . Collagen constitutes one to two percent of muscle tissue and accounts for 6% of the weight of strong, tendinous muscles. The is the most common cell that creates collagen. , which is used in food and industry, is collagen that has been irreversibly . Collagen has many medical uses in treating complications of the bones and skin.


The name ''collagen'' comes from the Greek (''kólla''), meaning "", and suffix -γέν, ''-gen'', denoting "producing".

Human types

Over 90% of the collagen in the is . However, as of 2011, 28 types of human collagen have been identified, described, and divided into several groups according to the structure they form. All of the types contain at least one . The number of types shows collagen's diverse functionality. * Fibrillar (Type I, II, III, V, XI) * Non-fibrillar ** (Fibril Associated Collagens with Interrupted Triple Helices) (Type IX, XII, XIV, XIX, XXI) ** Short chain (Type VIII, X) ** (Type IV) ** (Multiple Triple Helix domains with Interruptions) (Type XV, XVIII) ** MACIT (Membrane Associated Collagens with Interrupted Triple Helices) (Type XIII, XVII) ** Microfibril forming (Type VI) ** Anchoring fibrils (Type VII) The five most common types are: * : skin, , vasculature, organs, (main component of the organic part of bone) * : (main collagenous component of cartilage) * : reticulate (main component of s), commonly found alongside type I * : forms basal lamina, the epithelium-secreted layer of the * : cell surfaces, hair, and

Medical uses

Cardiac applications

The collagenous which includes the four rings, is histologically, elastically and uniquely bound to cardiac muscle. The cardiac skeleton also includes the separating septa of the heart chambers – the and the . Collagen contribution to the measure of summarily represents a continuous torsional force opposed to the of blood pressure emitted from the heart. The collagenous structure that divides the upper chambers of the heart from the lower chambers is an impermeable membrane that excludes both blood and electrical impulses through typical physiological means. With support from collagen, never deteriorates to . Collagen is layered in variable densities with smooth muscle mass. The mass, distribution, age and density of collagen all contribute to the required to move blood back and forth. Individual cardiac valvular leaflets are folded into shape by specialized collagen under variable . Gradual deposition within collagen occurs as a natural function of aging. Calcified points within collagen matrices show contrast in a moving display of blood and muscle, enabling methods of technology to arrive at ratios essentially stating blood in () and blood out (). Pathology of the collagen underpinning of the heart is understood within the category of .

Cosmetic surgery

Collagen has been widely used in cosmetic surgery, as a healing aid for burn patients for reconstruction of bone and a wide variety of dental, orthopedic, and surgical purposes. Both human and bovine collagen is widely used as dermal fillers for treatment of wrinkles and skin aging.Dermal Fillers , The Ageing Skin
. Retrieved on 21 April 2013.
Some points of interest are: # When used cosmetically, there is a chance of allergic reactions causing prolonged redness; however, this can be virtually eliminated by simple and inconspicuous ing prior to cosmetic use. # Most medical collagen is derived from young beef cattle (bovine) from certified -free animals. Most manufacturers use donor animals from either "closed herds", or from countries which have never had a reported case of BSE such as Australia, Brazil, and New Zealand.

Bone grafts

As the skeleton forms the structure of the body, it is vital that it maintains its strength, even after breaks and injuries. Collagen is used in bone grafting as it has a triple helical structure, making it a very strong molecule. It is ideal for use in bones, as it does not compromise the structural integrity of the skeleton. The triple helical structure of collagen prevents it from being broken down by enzymes, it enables adhesiveness of cells and it is important for the proper assembly of the extracellular matrix.

Tissue regeneration

Collagen scaffolds are used in tissue regeneration, whether in sponges, thin sheets, gels, or fibers. Collagen has favorable properties for tissue regeneration, such as pore structure, permeability, hydrophilicity, and stability in vivo. Collagen scaffolds also support deposition of cells, such as and s, and once inserted, facilitate growth to proceed normally.

Reconstructive surgical uses

Collagens are widely employed in the construction of substitutes used in the management of severe and wounds. These collagens may be derived from bovine, equine, porcine, or even human sources; and are sometimes used in combination with s, s, s, s and other substances.

Wound healing

Collagen is one of the body's key natural resources and a component of skin tissue that can benefit all stages of . When collagen is made available to the wound bed, closure can occur. Wound deterioration, followed sometimes by procedures such as amputation, can thus be avoided. Collagen is a natural product and is thus used as a natural wound dressing and has properties that artificial wound dressings do not have. It is resistant against bacteria, which is of vital importance in a wound dressing. It helps to keep the wound sterile, because of its natural ability to fight infection. When collagen is used as a burn dressing, healthy is able to form very quickly over the burn, helping it to heal rapidly. Throughout the four phases of wound healing, collagen performs the following functions in wound healing: * Guiding function: serve to guide fibroblasts. Fibroblasts migrate along a connective tissue matrix. * properties: The large surface area available on collagen fibers can attract fibrogenic cells which help in healing. * : Collagen, in the presence of certain neutral salt molecules can act as a nucleating agent causing formation of fibrillar structures. A collagen wound dressing might serve as a guide for orienting new collagen deposition and capillary growth. * properties: Blood s interact with the collagen to make a hemostatic plug.

Basic research

Collagen is used in for , studying cell behavior and cellular interactions with the .


The collagen protein is composed of a triple helix, which generally consists of two identical chains (α1) and an additional chain that differs slightly in its chemical composition (α2). The amino acid composition of collagen is atypical for proteins, particularly with respect to its high content. The most common motifs in the amino acid sequence of collagen are --X and glycine-X-hydroxyproline, where X is any amino acid other than , or . The average amino acid composition for fish and mammal skin is given.


First, a three-dimensional stranded structure is assembled, with the amino acids glycine and proline as its principal components. This is not yet collagen but its precursor, procollagen. Procollagen is then modified by the addition of groups to the amino acids and . This step is important for later and the formation of the triple helix structure of collagen. Because the hydroxylase enzymes that perform these reactions require as a cofactor, a long-term deficiency in this vitamin results in impaired collagen synthesis and . These hydroxylation reactions are catalyzed by two different enzymes: prolyl-4-hydroxylase and lysyl-hydroxylase. The reaction consumes one ascorbate molecule per hydroxylation. The synthesis of collagen occurs inside and outside of the cell. The formation of collagen which results in fibrillary collagen (most common form) is discussed here. Meshwork collagen, which is often involved in the formation of filtration systems, is the other form of collagen. All types of collagens are triple helices, and the differences lie in the make-up of the alpha peptides created in step 2. # Transcription of mRNA: About 44 genes are associated with collagen formation, each coding for a specific mRNA sequence, and typically have the "''COL''" prefix. The beginning of collagen synthesis begins with turning on genes which are associated with the formation of a particular alpha peptide (typically alpha 1, 2 or 3). # Pre-pro-peptide formation: Once the final mRNA exits from the cell nucleus and enters into the cytoplasm, it links with the ribosomal subunits and the process of translation occurs. The early/first part of the new peptide is known as the signal sequence. The signal sequence on the of the peptide is recognized by a on the endoplasmic reticulum, which will be responsible for directing the into the endoplasmic reticulum. Therefore, once the synthesis of new peptide is finished, it goes directly into the endoplasmic reticulum for post-translational processing. It is now known as preprocollagen. # Pre-pro-peptide to pro-collagen: Three modifications of the pre-pro-peptide occur leading to the formation of the alpha peptide: ## The signal peptide on the N-terminal is removed, and the molecule is now known as ''propeptide'' (not procollagen). ## Hydroxylation of lysines and prolines on propeptide by the enzymes 'prolyl hydroxylase' and 'lysyl hydroxylase' (to produce hydroxyproline and hydroxylysine) occurs to aid cross-linking of the alpha peptides. This enzymatic step requires as a cofactor. In , the lack of hydroxylation of prolines and lysines causes a looser triple helix (which is formed by three alpha peptides). ## Glycosylation occurs by adding either glucose or galactose monomers onto the hydroxyl groups that were placed onto lysines, but not on prolines. ## Once these modifications have taken place, three of the hydroxylated and glycosylated propeptides twist into a triple helix forming procollagen. Procollagen still has unwound ends, which will be later trimmed. At this point, the procollagen is packaged into a transfer vesicle destined for the Golgi apparatus. # Golgi apparatus modification: In the Golgi apparatus, the procollagen goes through one last post-translational modification before being secreted out of the cell. In this step, oligosaccharides (not monosaccharides as in step 3) are added, and then the procollagen is packaged into a secretory vesicle destined for the extracellular space. # Formation of tropocollagen: Once outside the cell, membrane bound enzymes known as collagen peptidases, remove the "loose ends" of the procollagen molecule. What is left is known as tropocollagen. Defects in this step produce one of the many collagenopathies known as . This step is absent when synthesizing type III, a type of fibrilar collagen. # Formation of the collagen fibril: , an extracellular enzyme, produces the final step in the collagen synthesis pathway. This enzyme acts on lysines and hydroxylysines producing aldehyde groups, which will eventually undergo covalent bonding between tropocollagen molecules. This polymer of tropocollagen is known as a collagen fibril.

Amino acids

Collagen has an unusual composition and sequence: * is found at almost every third . * makes up about 17% of collagen. * Collagen contains two uncommon derivative amino acids not directly inserted during . These amino acids are found at specific locations relative to glycine and are modified post-translationally by different enzymes, both of which require as a . ** derived from proline ** derived from – depending on the type of collagen, varying numbers of hydroxylysines are (mostly having s attached). stimulates of (skin) collagen into amino acids.

Collagen I formation

Most collagen forms in a similar manner, but the following process is typical for type I: # Inside the cell ## Two types of alpha chains – alpha-1 and alpha 2, are formed during on ribosomes along the (RER). These peptide chains known as preprocollagen, have registration peptides on each end and a . ## Polypeptide chains are released into the lumen of the RER. ## Signal peptides are cleaved inside the RER and the chains are now known as pro-alpha chains. ## of and amino acids occurs inside the lumen. This process is dependent on and consumes (vitamin C) as a . ## of specific hydroxylysine residues occurs. ## Triple alpha helical structure is formed inside the endoplasmic reticulum from two alpha-1 chains and one alpha-2 chain. ## is shipped to the , where it is packaged and secreted into extracellular space by . # Outside the cell ## Registration peptides are cleaved and tropocollagen is formed by . ## Multiple tropocollagen molecules form collagen fibrils, via covalent cross-linking () by which links hydroxylysine and lysine residues. Multiple collagen fibrils form into collagen fibers. ## Collagen may be attached to cell membranes via several types of protein, including , , and .

Synthetic pathogenesis

Vitamin C deficiency causes , a serious and painful disease in which defective collagen prevents the formation of strong . deteriorate and bleed, with loss of teeth; skin discolors, and s do not heal. Prior to the 18th century, this condition was notorious among long-duration military, particularly naval, expeditions during which participants were deprived of foods containing vitamin C. An such as or may attack healthy collagen fibers. Many bacteria and viruses secrete s, such as the enzyme , which destroys collagen or interferes with its production.

Molecular structure

A single collagen molecule, tropocollagen, is used to make up larger collagen aggregates, such as fibrils. It is approximately 300  long and 1.5 nm in diameter, and it is made up of three strands (called alpha peptides, see step 2), each of which has the conformation of a left-handed – this should not be confused with the right-handed . These three left-handed helices are twisted together into a right-handed triple helix or "super helix", a cooperative stabilized by many s. With type I collagen and possibly all fibrillar collagens, if not all collagens, each triple-helix associates into a right-handed super-super-coil referred to as the collagen microfibril. Each microfibril is with its neighboring microfibrils to a degree that might suggest they are individually unstable, although within collagen fibrils, they are so well ordered as to be crystalline. A distinctive feature of collagen is the regular arrangement of s in each of the three chains of these collagen subunits. The sequence often follows the pattern --X or Gly-X-, where X may be any of various other amino acid residues. Proline or hydroxyproline constitute about 1/6 of the total sequence. With glycine accounting for the 1/3 of the sequence, this means approximately half of the collagen sequence is not glycine, proline or hydroxyproline, a fact often missed due to the distraction of the unusual GX1X2 character of collagen alpha-peptides. The high glycine content of collagen is important with respect to stabilization of the collagen helix as this allows the very close association of the collagen fibers within the molecule, facilitating hydrogen bonding and the formation of intermolecular cross-links. This kind of regular repetition and high glycine content is found in only a few other fibrous proteins, such as silk . Collagen is not only a structural protein. Due to its key role in the determination of cell phenotype, cell adhesion, tissue regulation, and infrastructure, many sections of its non-proline-rich regions have cell or matrix association/regulation roles. The relatively high content of proline and hydroxyproline rings, with their geometrically constrained and (secondary) groups, along with the rich abundance of glycine, accounts for the tendency of the individual polypeptide strands to form left-handed helices spontaneously, without any intrachain hydrogen bonding. Because glycine is the smallest amino acid with no side chain, it plays a unique role in fibrous structural proteins. In collagen, Gly is required at every third position because the assembly of the triple helix puts this residue at the interior (axis) of the helix, where there is no space for a larger side group than glycine's single atom. For the same reason, the rings of the Pro and Hyp must point outward. These two amino acids help stabilize the triple helix – Hyp even more so than Pro; a lower concentration of them is required in animals such as fish, whose are lower than most warm-blooded animals. Lower proline and hydroxyproline contents are characteristic of cold-water, but not warm-water fish; the latter tend to have similar proline and hydroxyproline contents to mammals. The lower proline and hydroxproline contents of cold-water fish and other animals leads to their collagen having a lower thermal stability than mammalian collagen. This lower thermal stability means that derived from fish collagen is not suitable for many food and industrial applications. The tropocollagen spontaneously , with regularly staggered ends, into even larger arrays in the spaces of tissues. Additional assembly of fibrils is guided by fibroblasts, which deposit fully formed fibrils from fibripositors. In the fibrillar collagens, molecules are staggered to adjacent molecules by about 67  (a unit that is referred to as ‘D’ and changes depending upon the hydration state of the aggregate). In each D-period repeat of the microfibril, there is a part containing five molecules in cross-section, called the "overlap", and a part containing only four molecules, called the "gap". These overlap and gap regions are retained as microfibrils assemble into fibrils, and are thus viewable using electron microscopy. The triple helical tropocollagens in the microfibrils are arranged in a quasihexagonal packing pattern. There is some crosslinking within the triple helices, and a variable amount of covalent crosslinking between tropocollagen helices forming well organized aggregates (such as fibrils). Larger fibrillar bundles are formed with the aid of several different classes of proteins (including different collagen types), glycoproteins, and proteoglycans to form the different types of mature tissues from alternate combinations of the same key players. Collagen's was a barrier to the study of monomeric collagen until it was found that tropocollagen from young animals can be extracted because it is not yet fully . However, advances in microscopy techniques (i.e. electron microscopy (EM) and atomic force microscopy (AFM)) and X-ray diffraction have enabled researchers to obtain increasingly detailed images of collagen structure ''in situ''. These later advances are particularly important to better understanding the way in which collagen structure affects cell–cell and cell–matrix communication and how tissues are constructed in growth and repair and changed in development and disease. For example, using AFM–based nanoindentation it has been shown that a single collagen fibril is a heterogeneous material along its axial direction with significantly different mechanical properties in its gap and overlap regions, correlating with its different molecular organizations in these two regions. Collagen fibrils/aggregates are arranged in different combinations and concentrations in various tissues to provide varying tissue properties. In bone, entire collagen triple helices lie in a parallel, staggered array. 40 nm gaps between the ends of the tropocollagen subunits (approximately equal to the gap region) probably serve as nucleation sites for the deposition of long, hard, fine crystals of the mineral component, which is hydroxylapatite (approximately) Ca10(OH)2(PO4)6. Type I collagen gives bone its .

Associated disorders

Collagen-related diseases most commonly arise from genetic defects or nutritional deficiencies that affect the biosynthesis, assembly, postranslational modification, secretion, or other processes involved in normal collagen production. In addition to the above-mentioned disorders, excessive deposition of collagen occurs in .


One thousand mutations have been identified in 12 out of more than 20 types of collagen. These mutations can lead to various diseases at the tissue level. – Caused by a mutation in type 1 collagen, dominant autosomal disorder, results in weak bones and irregular connective tissue, some cases can be mild while others can be lethal. Mild cases have lowered levels of collagen type 1 while severe cases have structural defects in collagen. s – Skeletal disorder believed to be caused by a mutation in type 2 collagen, further research is being conducted to confirm this. – Thirteen different types of this disorder, which lead to deformities in connective tissue, are known. Some of the rarer types can be lethal, leading to the rupture of arteries. Each syndrome is caused by a different mutation. For example, the vascular type (vEDS) of this disorder is caused by a mutation in collagen type 3. – Can be passed on genetically, usually as X-linked dominant, but also as both an autosomal dominant and autosomal recessive disorder, sufferers have problems with their kidneys and eyes, loss of hearing can also develop during the childhood or adolescent years. – Caused by a mutation in the gene that codes for the production of collagen XVIII. Patients present with protrusion of the brain tissue and degeneration of the retina; an individual who has family members suffering from the disorder is at an increased risk of developing it themselves since there is a hereditary link.


Collagen is one of the long, whose functions are quite different from those of s, such as s. Tough bundles of collagen called ''collagen fibers'' are a major component of the that supports most tissues and gives cells structure from the outside, but collagen is also found inside certain cells. Collagen has great , and is the main component of , , s, s, and skin. Along with and soft , it is responsible for skin strength and elasticity, and its degradation leads to s that accompany . It strengthens s and plays a role in development. It is present in the and lens of the eye in line form. It may be one of the most abundant proteins in the fossil record, given that it appears to fossilize frequently, even in bones from the and .


Collagen has a wide variety of applications, from food to medical. For instance, it is used in and . It is widely used in the form of collagen for sausages. If collagen is subject to sufficient , e.g. by heating, the three tropocollagen strands separate partially or completely into globular domains, containing a different secondary structure to the normal collagen polyproline II (PPII), e.g. s. This process describes the formation of , which is used in many foods, including flavored s. Besides food, gelatin has been used in pharmaceutical, cosmetic, and photography industries. It is also used as a . From the Greek for glue, ''kolla'', the word collagen means " producer" and refers to the early process of boiling the skin and of horses and other animals to obtain glue. Collagen adhesive was used by Egyptians about 4,000 years ago, and Native Americans used it in about 1,500 years ago. The oldest glue in the world, as more than 8,000 years old, was found to be collagen – used as a protective lining on rope baskets and s, to hold together, and in crisscross decorations on s. Collagen normally converts to gelatin, but survived due to dry conditions. Animal glues are , softening again upon reheating, so they are still used in making s such as fine violins and guitars, which may have to be reopened for repairs – an application incompatible with tough, plastic adhesives, which are permanent. Animal sinews and skins, including leather, have been used to make useful articles for millennia. Gelatin-- glue (and with formaldehyde replaced by less-toxic pentanedial and ) has been used to repair experimental incisions in rabbit s.


The molecular and packing structures of collagen eluded scientists over decades of research. The first evidence that it possesses a regular structure at the molecular level was presented in the mid-1930s. Research then concentrated on the conformation of the collagen , producing several competing models, although correctly dealing with the conformation of each individual peptide chain. The triple-helical "Madras" model, proposed by in 1955, provided an accurate model of in collagen. This model was supported by further studies of higher resolution in the late 20th century. The packing structure of collagen has not been defined to the same degree outside of the collagen types, although it has been long known to be hexagonal. As with its monomeric structure, several conflicting models propose either that the packing arrangement of collagen molecules is 'sheet-like', or is lar. The microfibrillar structure of collagen fibrils in tendon, cornea and cartilage was imaged directly by in the late 20th century and early 21st century. The microfibrillar structure of tail tendon was modeled as being closest to the observed structure, although it oversimplified the topological progression of neighboring collagen molecules, and so did not predict the correct conformation of the discontinuous D-periodic pentameric arrangement termed ''microfibril''.

See also

* , a peptide that can bind to denatured collagen * * * , collagen-containing component of bone


{{Authority control Aging-related proteins