Facts about Collagen

Collagen is the most important structural protein in the human and animal body, accounting for about 30% of the total protein content. Due to its unique structure, it provides elasticity and strength to the connective tissue, cartilage, and intervertebral discs as well as to tendons, ligaments, and the skin.

Cartilage is particularly important for the mobility and health of joints.

Structure of Collagen

The structure of collagen fibers is comparable to that of a rope. Many individual fibers twist tightly around themselves and are then twisted together with others to form long strings. A stable rope structure is created by further twisting several cords together. Due to this repeatedly twisted structure, collagen fibers provide enormous tensile strength combined with low extensibility.

The primary structure of collagen fibers consists of individual, long chains of amino acids (protein building blocks). The spatial form of these chains is determined by sequence and binding of these amino acids. The amino acid sequence glycine-proline-hydroxyproline is quite frequent, leading to the formation of left-turning spirals (helices). This secondary structure of the whole protein is a kind of an α-chain. Three of these α-chains are twisted around themselves to form the so-called tertiary structure of the protein. The respective right-turning triple helix is called tropocollagen. Many of these tropocollagen fibers assemble into collagen fibrils (also called collagen fibers). Cross-links both within and between individual tropocollagen units stabilize the whole molecule leading to the so-called quaternary structure.

Depending on the function of a tissue, collagen fibrils are arranged either in parallel (e.g., for force transmission in tendons) or in a net (e.g., in the vitreous body of the eye). All tissues consist of cells and connecting structures. Various types of fibers (collagen fibers, elastic fibers, reticular fibers) together with the basic substance (various proteins, polysaccharides, and many other components in water) form a gel-like material, that fills up the space between the tissue cells.

The structure and composition of this gel-like material called extracellular matrix vary in different tissues. The strength of bones and teeth, for example, results from calcium deposits in the extracellular matrix.

There is a wide variety of collagen types in the various tissues of the human (or animal) body, which differ in their amino acid composition, chain length, and degree of cross-linking. At least 28 different types of collagen are known today. Of those, type I to IV are particularly widespread and extensively described for many tissues:

Collagen type I (fiber-forming): collagen fibers in tendons, skin, bones, fascias, fibrocartilage etc. It is the most common type of collagen in terms of quantity, and thus is the main constituent during production of collagen derived products.
Collagen type II (fiber-forming): a structure protein in various types of cartilage and the vitreous body of the eye
Collagen type III (fiber-forming): in the skin, the inner organs, and vessel walls, etc.
Collagen type IV (mesh-forming): component of the basement membrane, a three-dimensional boundary layer that encloses different cell types. It serves as a kind of a glue that keeps the tissue in its form.

A detailed overview on the collagen family is published by Sylvie Richard-Blum (2011). The extracellular matrix is described in detail in a publication by Ayad and colleagues (1998), or a publication by Frantz et al. (2010).

Other Important Proteins of the Extracellular Matrix

Elastin is a meshed fiber protein. It consists of various polypeptide subunits and is another important structural protein of the human body. Elastin is present in large quantities in the skin, lungs, and blood vessels and gives these organs their characteristic elastic properties.

The structure of elastin is comparable to that of collagen, although the polypeptide chains of elastin contain a different amino acid composition. The cross-linking of these polypeptide chains produces a rubber-like elastic mesh that is responsible for the elasticity and deformability of the resulting structure. The combination of collagen and elastin makes a tissue both elastic and tear-proof, as the properties of the two structural proteins complement each other.

Hyaluronic acid is another important component of the extracellular matrix. It consists of long chains of specific sugar molecules and occurs in high concentrations in cartilage, intervertebral discs, skin, and synovial fluid (synovia). A special feature of hyaluronic acid is its ability to bind large amounts of water. The vitreous body of the human eye consists of 98 percent water, which is bound to only two percent hyaluronic acid [Berke 1999, Axenfeld 1980].

Articular Cartilage

The musculoskeletal system of humans and mammals is based on active and passive components. The skeletal bones and their connecting structures, such as cartilage, ligaments, and tendons belong to the passive components. The skeletal muscles are active components that are able to perform movement.

High mechanical stress builds up between individual bones during movement, especially in the areas of the knees and the back. Therefore, cartilage tissue covers the surface of all joints to protect the bone ends at their contact points. This cartilage layer provides a cushioning effect for low-friction motion.

Articular cartilage is composed of hyaline cartilage which is very resistant to pressure. Other types of cartilage are found in further tissues, such as highly shear-resistant fibrocartilage in intervertebral discs and meniscus, or flexible elastic cartilage in the auricle.

Cartilage tissue consists of cartilage cells (chondrocytes) surrounded by a specific extracellular matrix. Its basic substance contains a net of collagen fibrils (mainly of collagen type II). Together with other components, such as hyaluronic acid, this mesh-like structure is able to bind and store large amounts of water. This results in an elastic cartilage tissue with high pressure elasticity and strong load-bearing capacity.

Cartilage Damage

All healthy tissues are constantly being built up and broken down. In addition to repairing and renewing their structures, this allows the tissues to adapt to changing stress, such as that experienced during physical activity.

Chondrocytes are constantly producing extracellular matrix at a high output rate, thereby keeping the entire cartilage sound and healthy. Since cartilage tissue does not form blood vessels, it must be fed by passive transport (diffusion) either from the covering layer (perichondrium) or the synovial fluid (synovia). A healthy structure and regular movement of the joints is, therefore, crucial for the sufficient supply of nutrients to cartilage tissue.

The sensitive structure of cartilage may face an imbalance when tissue degradation outweighs the building-up process in diseases. Such cartilage damage can be caused by trauma (e.g., accidents) as well as overwork (e.g., extensive physical activity).
In addition, immobility due to low physical activity, permanent seated position, or undue load distribution also hinders the exchange of nutrients and metabolites, promoting the decay of cartilage tissue.

Unlike muscle tissue, articular cartilage does not spontaneously regenerate after damage. Therefore, defects remain and may even expand over time. Although cartilage tissue may be regenerated to a certain extent, this occurs via another mechanism which is different from the daily process of building up and breaking down. There is no formation of new cartilage cells within the joints, nor cell migration. Instead, regeneration involves the formation of cartilage tissue derived from the surface layer of the joint (perichondrium).

During impaired nutrition of the cartilage, the cartilage matrix is degraded and cartilage cells die, especially in previously damaged tissue. This results in clinically detectable osteoarthritis, among other diseases.

Osteoarthritis is the most common joint disease worldwide (Arden 2006) and quite often affects the heavily stressed knee joint. In Germany, around 5 million patients suffer from osteoarthritis according to the German association of osteoarthritis (Deutsche Arthrose Hilfe). In most cases, the disease becomes clinically apparent from the age of 45 onwards (Federal Statistical Office Germany).

Our current level of knowledge does not facilitate the cure of pronounced osteoarthritis associated with destroyed cartilage structures. However, optimal nutrition of cartilage with Bioactive Collagen Peptides may shift the collagen balance from degradation to that of building-up. In a best-case scenario, the development of osteoarthritis is completely avoided. The progression of existing osteoarthritis may be significantly reduced, as could the negative effects of pain, mobility, and other resulting disabilities.

Since osteoarthritis leads to considerable functional losses in the long term, cartilage regeneration is an important issue of clinical research. Therefore, all known orthopaedic, surgical, and nutritional measures are aimed at maintaining and restoring the cartilage matrix.

Last update: January 2018