Extracellular Matrix: Components, Functions & Cell Adhesion
Extracellular Matrix (ECM) Components
Glycosaminoglycans and Proteoglycans
Glycosaminoglycans (GAGs): Long, unbranched polysaccharide chains composed of repeating disaccharide units. They are usually sulfated and contain carboxyl groups, giving them a strong negative charge that attracts cations like Na+. This high concentration of Na+ and the inability of GAGs to fold into compact structures create tissue fluid drag, contributing to the ECM’s resistance to compression forces and providing intrinsic turgor to tissues. There are seven main groups of GAGs: hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, heparan sulfate, heparin, and keratan sulfate.
Proteoglycans: Macromolecules with a core protein and various sulfated GAGs projecting from its surface. Their spatial organization and GAG composition facilitate targeted delivery of molecules and allow variability in the pore size of the ECM gel. Their tissue distribution reflects local requirements for molecular pore size and specific charges.
Extracellular Structural Proteins
1. Laminin: A sulfated glycoprotein composed of three polypeptide chains, forming a cross-shape. It is a major component of the basal lamina, produced by most epithelial cells, and enables interaction between cells and the ECM.
2. Entactin: A sulfated glycoprotein found in the basal lamina, produced by most epithelial cells. It has binding sites for laminin and collagen type IV, acting as a liaison protein.
3. Tenascin: A nonfibrillar glycoprotein consisting of six polypeptide chains, resembling a spider with radially projecting legs. It is mainly expressed in embryonic tissues and is involved in cell adhesion and migration.
Other Substances
Water, ions, salts, serum proteins, catabolism products, vitamin C, etc.
Specialized Extracellular Matrix: Basal Lamina
Concept: A thin layer of specialized ECM synthesized by associated cellular elements, supporting all epithelial cells and surrounding fat, muscle, and Schwann cells. It provides an interface between parenchymal cells and stroma.
Content: Collagen type IV, fibronectin, proteoglycans, and structural glycoproteins.
Molecular Structure: Collagen type IV forms stacked polygonal networks that act as a framework for other components.
Microscopic Structure: Appears as a homogeneous, electron-dense band, visible with silver impregnation or PAS staining (basement membrane).
Functions: Provides adhesion between parenchymal cells and stroma, acts as a molecular sieve, controls cellular differentiation, and organizes interactions between cell surface receptors and ECM molecules.
Cell Adhesion to the ECM
Cell adhesion to the ECM occurs through:
- Hemidesmosomes: Anchor the intermediate filament cytoskeleton to the basal lamina.
- Integrins: Transmembrane proteins similar to receptors, but more numerous and with weaker bonds to ECM proteins. They are glycoprotein heterodimers composed of α and β chains, with the amino ends attaching to ECM molecules.
- Non-integrin glycoproteins: Generically called CAMs, they bind to collagen and other components.
Organization and Common Varieties of Connective Tissue
Content:
- Cells: Mesenchymal cells, fibroblasts, adipocytes, or migrating cells.
- Fibers: Collagen, elastic, reticular.
- Amorphous ground substance.
- Interstitial fluid.
Varieties:
- Mesenchymal: Found in embryos, with mesenchymal cells forming a network, no fibers, and abundant, sticky ground substance.
- Mucosal: Found in the umbilical cord, placental villi, and young dental pulp. It is jelly-like, with small cells and predominantly amorphous ground substance.
- Lax or Areolar: Tissue constituents are well-represented and in harmonious proportions. It is the most widespread variety, sometimes containing abundant adipocytes.
- Elastic: Elastic fibers predominate. Found in the spinal ligament, aorta walls, elastic lamina of arteries, suspensory ligaments, and vocal cord ligaments.
- Reticular: Composed of reticular fibers forming a mesh and reticular cells of fibroblastic, histiocytic, or antigen-presenting lineages. It supports parenchyma in the liver, bone marrow, and lymphoid organs.
- Dense: The fibrillar component is prominent, with relatively scarce cells and amorphous ground substance. Found in tendons, ligaments, organ capsules, fascia, muscle, dura, dermis, and corneal stroma. It has two subvariants: ordered (e.g., tendons, corneal stroma) and unordered (e.g., deep dermis).
