Extracellular Matrix (ECM): Structure, Function, and Components
TISSUE: Introduction: ECM is a complex network of macromolecules that acts as “cement” between the universal biological cells, as part of highly specialized structures: cartilage, tendons, bones, etc. This function supports the ECM’s role in regulating the behavior of cells that contact it, influencing their differentiation, development, migration, and shape. The ECM is produced by ECM-producing cells called connective tissue, connective, or supportive cells.
Supporting tissues: broadly refer to the ECM and the cells embedded within it, regardless of their occurrence. ECM-producing cells: are mainly derived from the mesoderm, with some originating from the ectoderm. They share structural features and have cell adhesion mechanisms that interact with ECM materials instead of other cells. They represent fixed cell populations in the supporting tissues, where the ECM is the predominant component.
1. Mesenchymal cells: morphologically, these are stellate cells with long, thin extensions that make contacts with one another, forming a mesh-like network. They are located in the embryonic mesenchyme. In adults, multipotent mesenchymal cells remain, mainly situated in the vicinity of blood vessels, called adventitial cells. Due to their function, it is more appropriate to refer to them as stem cells. Functionally, they have a high mitotic index, and their most prominent property is their multipotency for differentiation.
2. Fibroblasts: Concept and location: These are common, tissue-specific cells responsible for the synthesis of the ECM. They are known as fully differentiated ECM-producing cells. Structurally: they exhibit a stellate morphology in culture and a fusiform shape in tissues. The nucleus is large and central, and the cytoplasm is PAS-positive for secretion. Functionally: they synthesize ECM, resist aggression, are able to divide actively, participate in tissue repair, and can be transformed into histiocytes, fat cells, smooth muscle cells, etc. Types:
- Myofibroblasts: share typical features with fibroblasts and smooth muscle cells. They are located in the adrenal glands, testes, seminiferous tubules, etc.
- Pericytes: located in the walls of some venules and capillaries, they are involved in the elaboration of the basal lamina of the capillary or venule.
3. Chondroblasts/cytes: Concept and location: These are cells of chordoid tissue that produce specific ECM. When they stop actively synthesizing ECM, they are called chondrocytes. Their origin is ectodermal. Structurally: they resemble epithelial cells, with little intercellular substance mediating between them.
4. Chondroblasts/cytes: Concept and location: These are the cells of cartilage that produce the specific ECM, which is solid and non-mineralized. When they stop synthesizing ECM, they are called chondrocytes. Structurally: chondroblasts have a round or oval morphology, with a central nucleus and loose chromatin. Chondrocytes exhibit a variable appearance and are housed in condroplasmas carved for themselves in the ECM. All cells of an isogenic group come from the division of a single chondroblast, and their disposition depends on the planes of division.
5. Osteoblasts/cytes: Concept and location: These are the ECM-secreting cells in bone tissue. The newly formed material, the osteoid matrix, is quickly transformed into bone by the deposition of calcium phosphate salts. Structurally: osteoblasts have an epithelial appearance and signs of high metabolic activity, being located on the bone-forming surfaces. Osteocytes are cells endowed with fine processes and long extensions, with an oval nucleus and dense cytoplasm poor in organelles. Lysosomes highlight the enzymes that are discharged into the bone matrix to carry out the process of osteolysis. Osteocytes are important in regulating phospho-calcium balance.
6. Cells producing ECM in dental tissues:
- Ameloblasts: enamel
- Odontoblasts: dentin
- Cementoblasts: cement
Except for ameloblasts, which are derived from ectoderm, the rest are derived from mesoderm.
Macromolecules of the Extracellular Matrix:
A) Fibrillar proteins:
1. Collagen: (* Concept and general) Its amino acid composition is unique in the body, emphasizing glycine, proline, and hydroxyproline. Collagen molecules biochemically consist of tropocollagen subunits: ?-helical structures with three coiled polypeptide chains. (* Types):
- Type 1: Two chains ? 1 subtype and one chain ? 2. It is located in the deep dermis, tendons, and bones, forming high-strength fibers.
- Type 2: Three chains ? 1. It is found in cartilage, forming fibers.
- Type 3: Three chains ? 1. It appears in fetal skin, forming collagen and reticular fibers.
- Type 4: Three chains ? 1. It is found in the basal lamina, forming meshes.
- Type 5: Two chains ? 1, ? V, and chain ? 2. It appears in small numbers and diffuse distribution in the tissues, forming thin fibers.
- Type 6: Three chains ? 1, ? V. It forms thin fibrils.
- Type 7: Short and striated fibrils that are anchored in the basal lamina of the skin.
(* Synthesis): Collagenogenesis starts in ECM-producing cells. The polymerization of protein subunits to form fibrils and fibers occurs in the extracellular medium. The subunits of tropocollagen, when polymerized, form collagen fibrils, which, when added together, form thicker fibers. The formation of collagen fibers depends on the amino acids located at the ends of the tropocollagen molecule.
(* Collagen fibers) appear white and beam-forming, with an undulating course. They have very high tensile strength, are flexible, and slightly elastic. They are found in the supporting tissues of organisms that must withstand large tensile stresses. They are seen scattered, swirling, and in fascicles. A fiber results from the aggregation of microfibrils with cross-striations.
(* Reticular fibers) are collagen protein microfibrils coated with carbohydrates and lipids that prevent them from aggregating to form fibers of larger caliber. They have a tendency to form networks and are located in the liver, bone marrow, and lymphoid organs.
2. Fibrillin: A fibril-forming glycoprotein that is the PRINCIPAL component of extracellular microfibrils. It is associated with elastin and is secreted, organizing to form elastic fibers. It is detected in the mesangium of renal glomeruli and the spleen.
3. Elastin: (* Concept and general) An insoluble fibrous protein whose structural unit is tropoelastin. Its composition includes cysteine, proline, and glycine. Elastogenesis happens after the establishment of cross-bridges between tropoelastin molecules, giving rise to the formation of desmosine and lysine-Norleucine isodesmosine.
(* Elastic fibers): Their formation occurs by interaction between elastin and fibrillin, so that fibrillin microfibrils secreted elastin organized, which is deposited among those to be individualistic forming fibers. Their most prominent physical property is elasticity. They may be arranged in networks, parallel sheets, or bundles. They stain poorly, appearing little more or less homogeneously electron dense and consisting of tropoelastin microfilaments.
4. Fibronectin: A fiber-forming glycoprotein consisting of two chains linked by disulfide bonds. It appears in the ECM in aggregates. It is involved in mechanisms of cell adhesion and cell migration during embryonic development. It has the ability to bind to various components of tissues, such as collagen, heparin, etc. In cell membranes, there are receptors belonging to the generic group of integrins that bind to fibronectin. It participates in the orientation of collagen fibrils and the arrangement of macromolecular proteoglycan networks.