Collagen Types and Structure
- Over 90% of the collagen in the human body is type I collagen.
- 28 types of human collagen have been identified and divided into several groups based on their structure.
- All types of collagen contain at least one triple helix.
- Collagen forms a stable structure through hydrogen bonds and associates into a right-handed super-super-coil called the collagen microfibril.
- Three polypeptides coil to form tropocollagen, which then bind together to form a fibril and further form a fiber.
- Collagen has a regular arrangement of amino acids, with a sequence often following the pattern Gly-Pro-X or Gly-X-Hyp.
- Proline and hydroxyproline constitute about 1/6 of the total sequence, while glycine accounts for 1/3 of the sequence.
- Collagen fibrils have a distinctive D-period repeat of approximately 67nm, resulting in visible bands under electron microscopy.
- Covalent crosslinking occurs within the triple helices and between tropocollagen helices, forming well-organised aggregates.
- Collagen derived from cold-water fish has lower proline and hydroxyproline contents, leading to lower thermal stability compared to mammalian collagen.
Collagen Synthesis and Formation
- Collagen synthesis involves the modification of procollagen, which is formed by the addition of hydroxyl groups to proline and lysine amino acids.
- Hydroxylation reactions are catalyzed by prolyl-4-hydroxylase and lysyl-hydroxylase enzymes.
- Vitamin C is required as a cofactor for these hydroxylation reactions.
- The synthesis of collagen occurs both inside and outside the cell.
- Transcription of mRNA is initiated for the formation of a specific alpha peptide associated with collagen.
- Pre-pro-peptide formation occurs as the mRNA is translated and the signal sequence directs the peptide into the endoplasmic reticulum.
- Pre-pro-peptide is modified to propeptide by removing the signal peptide and undergoing hydroxylation of lysines and prolines.
- Glycosylation takes place by adding glucose or galactose monomers onto the hydroxyl groups of lysines.
- Procollagen is formed when three hydroxylated and glycosylated propeptides twist into a triple helix structure.
- In the Golgi apparatus, procollagen undergoes post-translational modification.
- Oligosaccharides are added to the procollagen.
- The modified procollagen is packaged into secretory vesicles for extracellular secretion.
- Defects in this step can lead to collagenopathies like Ehlers-Danlos syndrome.
- The procollagen is further processed and trimmed before being secreted.
- Tropocollagen is formed outside the cell by removing the loose ends of procollagen.
- Collagen peptidases are responsible for this removal process.
- The remaining tropocollagen undergoes covalent bonding between molecules through lysyl oxidase.
- Lysyl oxidase produces aldehyde groups on lysines and hydroxylysines.
- Multiple tropocollagen molecules form collagen fibrils, which eventually form collagen fibers.
Collagen Functions and Applications
- Collagen plays a key role in determining cell phenotype, cell adhesion, tissue regulation, and infrastructure.
- Non-proline-rich regions of collagen have roles in cell or matrix association/regulation.
- Collagen's unique properties make it important in various biological processes and tissue construction.
- Collagen scaffolds, such as sponges, thin sheets, gels, and fibers, are used in tissue regeneration.
- Collagen scaffolds have favorable properties for tissue regeneration, including pore structure, permeability, hydrophilicity, and in vivo stability.
- Collagen scaffolds support the deposition and growth of cells like osteoblasts and fibroblasts.
- Collagens are widely used in the construction of artificial skin substitutes for severe burns and wounds.
- Artificial skin substitutes containing collagen aid in wound healing and management.
- Collagen-based dressings have unique properties, including resistance against bacteria and promotion of rapid healing.
- Collagen is a key component of skin tissue and supports all stages of wound healing.
- Availability of collagen in the wound bed promotes wound closure and prevents deterioration.
- Collagen serves as a natural wound dressing, providing properties that artificial dressings lack.
- Collagen resists bacterial infection and helps maintain a sterile wound environment.
- Collagen promotes rapid healing of burns by facilitating the formation of healthy granulation tissue.
Collagen Types and Disorders
- Collagen-related diseases often arise from genetic defects or nutritional deficiencies affecting collagen production.
- Genetic defects in collagen genes can lead to disorders such as Osteogenesis imperfecta, Ehlers-Danlos syndrome, and Caffeys disease.
- Different collagen types are associated with specific disorders, such as types II and XI collagenopathies.
- Excessive collagen deposition occurs in scleroderma.
- Mutations in collagen genes can result in various diseases at the tissue level.
Collagen Research and Advances
- Collagen's insolubility was initially a barrier to its study, but extraction from young animals allowed for research breakthroughs.
- Advances in microscopy techniques and X-ray diffraction have provided detailed images of collagen structure.
- Understanding collagen structure is crucial for studying cell-cell and cell-matrix communication, tissue growth and repair, and developmental changes.
- Nanoindentation studies have revealed the heterogeneous nature of collagen fibrils and their different mechanical properties in gap and overlap regions.
- Collagen's arrangement and concentration vary in different tissues to provide specific tissue properties, such as bone's tensile strength.