Collagen structure
COLLAGEN
Reviewing collagen formation provides an appreciation of how collagen accounts for the viscosity of gelatinous structures, the toughness of deep fascia, and the tenacity of scar tissue adhesions. To understand the dynamics of scar tissue adhesions during wound healing, it is helpful to review the biochemistry and biomechanical behavior of collagen and its interaction with other macromolecules in the ECM ( Extracellular matrix ). |
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Where is the synthesis of collagen ?
Collagen synthesis begins in the rough endoplasmic reticulum of connective tissue fibroblasts. In the intracellular endoplasmic reticulum, a repeating sequence of specific amino acids is assembled into long polypeptide chains of uniform length. The amino acid sequence of assembled peptide chains has a characteristic pattern of glycine-X-Y. Every third amino acid residue is glycine, and either proline or lysine amino acids are in the X-Y position on the peptide chain. Disruption of the glycine-X-Y amino acid sequence, such as occurs in osteogenesis imperfecta, leads to loss of the mechanical properties of collagen. Three polypeptide chains attach in a right-handed triple helix formation to form the procollagen molecule. Because of the three-dimensional shape of each chain and the relative placement of radicals that react with each other through hydrophobic, hydrophilic, hydrogen, and covalent interactions, the chains fit together in specific configurations of fixed dimensions with uniform length and width.
The procollagen molecule now has a rod-like structure of approximately 300 nm in length and 1.5 nm in diameter,Once procollagen molecule is extruded from the fibroblast into the interstitial space of the DCT ( Dens-Connective Tissue ) matrix, cleavage at terminal sites of the molecule occurs and the nonhelical ends are removed. The slightly shortened molecule is now called tropocollagen, known as the basic building block of collagen.
Five tropocollagen molecules rapidly aggregate in an overlapping array to form a collagen microfibril. Groups of microfibrils organize into the subfibril, and subfibrils combine to form fibrils. Assembly of the collagen fibril takes place as a complex interaction between the tropocollagen molecules, the fibroblast cell membrane surface, and the GAGs, PGs, and glycoproteins of the ECM. It is at the level of the collagen fibril that the characteristic periodicity or cross-banding observed in x-ray diffraction and electron microscopic studies is demonstrated This periodicity is the result of the specific overlapping and stacking of the tropocollagen molecules within the larger units, emphasizing the highly structured molecular organization of collagen. The physical and mechanical properties of collagen, giving it the ability to withstand tensile loads, are governed directly by this hierarchy of organization.
Collagen synthesis begins in the rough endoplasmic reticulum of connective tissue fibroblasts. In the intracellular endoplasmic reticulum, a repeating sequence of specific amino acids is assembled into long polypeptide chains of uniform length. The amino acid sequence of assembled peptide chains has a characteristic pattern of glycine-X-Y. Every third amino acid residue is glycine, and either proline or lysine amino acids are in the X-Y position on the peptide chain. Disruption of the glycine-X-Y amino acid sequence, such as occurs in osteogenesis imperfecta, leads to loss of the mechanical properties of collagen. Three polypeptide chains attach in a right-handed triple helix formation to form the procollagen molecule. Because of the three-dimensional shape of each chain and the relative placement of radicals that react with each other through hydrophobic, hydrophilic, hydrogen, and covalent interactions, the chains fit together in specific configurations of fixed dimensions with uniform length and width.
The procollagen molecule now has a rod-like structure of approximately 300 nm in length and 1.5 nm in diameter,Once procollagen molecule is extruded from the fibroblast into the interstitial space of the DCT ( Dens-Connective Tissue ) matrix, cleavage at terminal sites of the molecule occurs and the nonhelical ends are removed. The slightly shortened molecule is now called tropocollagen, known as the basic building block of collagen.
Five tropocollagen molecules rapidly aggregate in an overlapping array to form a collagen microfibril. Groups of microfibrils organize into the subfibril, and subfibrils combine to form fibrils. Assembly of the collagen fibril takes place as a complex interaction between the tropocollagen molecules, the fibroblast cell membrane surface, and the GAGs, PGs, and glycoproteins of the ECM. It is at the level of the collagen fibril that the characteristic periodicity or cross-banding observed in x-ray diffraction and electron microscopic studies is demonstrated This periodicity is the result of the specific overlapping and stacking of the tropocollagen molecules within the larger units, emphasizing the highly structured molecular organization of collagen. The physical and mechanical properties of collagen, giving it the ability to withstand tensile loads, are governed directly by this hierarchy of organization.
Bundles of collagen fibrils combine to form connective tissue fascicles. It is at the level of the DCT fascicle that a tendon or ligament can first be tested mechanically. Whenever subjected to stress during formation, these fascicles form with a distinct waveform, know as crimp. Crimping occurs in all biologic collagenous tissues that undergo tension. The acute angle of crimping of collagen at this level of DCT development is 15 to 20° and is both predictable and measurable. The compliance of DCT is primarily, therefore, a function of removing the crimp or increasing the angle of crimping. In other words, when working within physiologic limits, collagen can be elongated temporarily with the straightening of the crimped DCT fascicles. However, as a result of the dimensions set by the molecular attachments, native collagen cannot shrink or be stretched with “permanent” elongation. Clinically speaking, any permanent elongation signifies tearing or denaturing of the collagenous structure with irreversible damage. Collagen fascicles combine to make up the gross structure of tendon, ligament, and joint capsule As presented, collagen is a complex structure.
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Nineteen types of collagen have been identified and categorized into six distinct classes based on the differences in their structure, location, and function. much of the biomechanical properties of DCT, however, have been studied on the fibril-forming collagens , made up predominantly of collagen types I, II, and III Tendons and ligaments are examples of those fibril-forming collagens whose primary function is to resist tensile forces. The larger structural, interstitial fibers of tendons and ligaments contain mostly type I collagen and, in smaller quantities, type II collagen. Articular cartilage, bone, dermis, and intervertebral disks are tissues that require resistance to applied tensile loads. Articular cartilage is typically composed of type II collagen, whereas bone, dermis, and fibrous cartilage (intervertebral disk) is type I. Type III collagen is found in expansible organs such as arteries, uterus,liver, spleen, kidney, and lungs and serves a structural support function.
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CLINICAL CONSIDERATIONS
The collagen microfibril has been termed a “crystallite” structure because of the consistent spatial relationship of its molecules. Collagen, therefore, is an organic crystal. The significance of these dimensions set by molecular attachments is that native collagen cannot shrink and cannot be stretched with permanent elongation, without denaturing or damaging the integrity of the soft tissue structure. comfortable working within the physiologic range of DCT if the treatment goal is not to tear or permanently damage a particular collagenous structure. One indication that the treatment is working outside the physiologic range, or “safe zone,” is when the client complains of prolonged stiffness, pain, or both lasting longer than 1 hour after treatment.
Maturation Changes in Collagen:
There are progressive changes in bonding as the collagen ages and matures. Once the tropocollagen molecules aggregate into microfibrils, gradual chemical changes occur resulting in the conversion of unstable hydrogen bonds into stable covalent bonds. New attachments are formed simultaneously with the organic molecules (GAGs) of the ground substance that result in additional stability.
The collagen microfibril has been termed a “crystallite” structure because of the consistent spatial relationship of its molecules. Collagen, therefore, is an organic crystal. The significance of these dimensions set by molecular attachments is that native collagen cannot shrink and cannot be stretched with permanent elongation, without denaturing or damaging the integrity of the soft tissue structure. comfortable working within the physiologic range of DCT if the treatment goal is not to tear or permanently damage a particular collagenous structure. One indication that the treatment is working outside the physiologic range, or “safe zone,” is when the client complains of prolonged stiffness, pain, or both lasting longer than 1 hour after treatment.
Maturation Changes in Collagen:
There are progressive changes in bonding as the collagen ages and matures. Once the tropocollagen molecules aggregate into microfibrils, gradual chemical changes occur resulting in the conversion of unstable hydrogen bonds into stable covalent bonds. New attachments are formed simultaneously with the organic molecules (GAGs) of the ground substance that result in additional stability.
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The end result is that the aging collagen becomes progressively rigid and strong. In addition to the increase in covalent bonding, two other factors thought to affect collagen strength during maturation include the continuous increase in size of the collagen fibers and the alignment of fibers along lines of stress. Stress as a physical stimulus is a significant factor in the formation and maintenance of collagen in DCT.
What are the mechanical properties of the collagen ?
The mechanical behavior of tendon and other DCT can be studied by elongating collagen fibers to the point of rupture.
The resulting changes in length and tension during stretch can be plotted to produce a stress–strain curve. Stress is the amount of load or tension per unit cross-sectional area placed on the specimen, whereas strain refers to the temporary elongation that occurs when stress is applied within physiologic limits.
Stress–Strain Curve
A stress–strain curve characteristic for tendon mechanically strained to the point of rupture includes five distinct regions:
1. Toe region: In the toe region, there is little increase in load with lengthening. This region represents a 1.2 to 2% strain, and occurs during loading for 1 hour or less. The load stays within the physiologic limit of the tissue. The crimp is temporarily removed at the level of the DCT fascicle without permanently denaturing or damaging the tendon, thus allowing the treatment to remodel the connective tissue along lines of stress.
2. Linear region: In the linear region, increased elongation requires disproportionately larger amounts of stress. Microfailure of the tendon begins early in this region, plotted as a 2 to 6% strain. Clinically, the patient complains of tendon stiffness, a clue that treatment was slightly outside the physiologic range for working with collagenous tissues.
3. Region of progressive failure: In this region, the slope of the stress–strain curve begins to decrease, indicating microscopic disruption of sufficient amounts of DCT structure. The gross tendon, nonetheless, appears to be normal and intact. An observed decrease in the slope angle on the stress–strain curve is called yield and occurs around 6% strain.
4. Region of major failure: The slope of the stress–strain curve now flattens dramatically. Although the gross tendon is intact, there is visible narrowing at numerous points of shear and rupture. This narrowing at points of tear, demonstrated between 6 and 12% strain on the curve, is known as necking.
What are the mechanical properties of the collagen ?
The mechanical behavior of tendon and other DCT can be studied by elongating collagen fibers to the point of rupture.
The resulting changes in length and tension during stretch can be plotted to produce a stress–strain curve. Stress is the amount of load or tension per unit cross-sectional area placed on the specimen, whereas strain refers to the temporary elongation that occurs when stress is applied within physiologic limits.
Stress–Strain Curve
A stress–strain curve characteristic for tendon mechanically strained to the point of rupture includes five distinct regions:
1. Toe region: In the toe region, there is little increase in load with lengthening. This region represents a 1.2 to 2% strain, and occurs during loading for 1 hour or less. The load stays within the physiologic limit of the tissue. The crimp is temporarily removed at the level of the DCT fascicle without permanently denaturing or damaging the tendon, thus allowing the treatment to remodel the connective tissue along lines of stress.
2. Linear region: In the linear region, increased elongation requires disproportionately larger amounts of stress. Microfailure of the tendon begins early in this region, plotted as a 2 to 6% strain. Clinically, the patient complains of tendon stiffness, a clue that treatment was slightly outside the physiologic range for working with collagenous tissues.
3. Region of progressive failure: In this region, the slope of the stress–strain curve begins to decrease, indicating microscopic disruption of sufficient amounts of DCT structure. The gross tendon, nonetheless, appears to be normal and intact. An observed decrease in the slope angle on the stress–strain curve is called yield and occurs around 6% strain.
4. Region of major failure: The slope of the stress–strain curve now flattens dramatically. Although the gross tendon is intact, there is visible narrowing at numerous points of shear and rupture. This narrowing at points of tear, demonstrated between 6 and 12% strain on the curve, is known as necking.
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5. Region of complete rupture: The slope of the stress–strain curve falls off, indicating a total break in the gross tendon. Tendon failure occurs with 12 to 15% strain. When a load is removed from a tendon before incomplete rupture, the tendon returns to its original starting length after a period of rest. The return of the temporarily elongated tendon to its original length is called recovery. Being a crystalline structure, collagen can be deformed temporarily by stress when working within physiologic limits, but with the removal of the load the collagen recovers to its original length.
