Extracellular Matrix Components: Elastin, Fibronectin, Glycosaminoglycans and Basal Lamina

Elastin: Concept and Generalities

Elastin is a fibrous, insoluble structural protein, similar to tropoelastin. Its composition is rich in valine, proline and glycine. During elastogenesis, lysyl oxidase cross-links molecules of tropoelastin, resulting in the formation of desmosine, isodesmosine and lysinonorleucine.

Elastic Fibers

The formation of elastic fibers results from the interaction between elastin and fibrillin microfibrils. Elastin is deposited onto an organized fibrillin scaffold, and the fibers aggregate forming elastic fibers. Elastin has a distinctive physical property: elasticity. Fibers can form networks, sheets or fascicles. They do not stain with common dyes, but they can be stained with orcein or resorcin-fuchsin, appearing as a homogeneous, dense material under the microscope.

Fibronectin

Fibronectin is a fiber-forming glycoprotein consisting of two chains linked by disulfide bonds. It appears in the extracellular matrix in the form of aggregates and is involved in cell adhesion and cell migration during embryonic development. It has the ability to bind various tissue components, such as collagen and heparin. In cell membranes there are receptors belonging to the integrin family that bind fibronectin. It is involved in the orientation of collagen fibrils and in the arrangement of macromolecular proteoglycans.

b.) Glycosaminoglycans and Proteoglycans

Glycosaminoglycans: These consist of long, unbranched heteropolysaccharide chains composed of repeating disaccharide units. They are sulfated and contain carboxyl groups, so they carry a negative charge that attracts positive cations such as Na⁺. The high concentration of Na⁺ and GAGs in the tissue fluid contributes to their hydration, which gives tissues resistance to compressive forces and intrinsic turgor. GAGs are divided into 7 groups: hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, keratan sulfate, heparan sulfate and heparin.

Proteoglycans: These are macromolecules that occupy large domains. The protein core is attached to a large number of sulfated GAG chains, which project into the three-dimensional space around them. Their spatial organization and charge allow selective diffusion of different molecules. Their variability allows the extracellular matrix to adapt in size and distribution to the specific needs of each tissue, with specific molecular charges and sizes.

c.) Extracellular Structural Proteins

1. Laminin: A sulfated glycoprotein formed by three polypeptide chains linked in a cross shape. It does not form fibers. It is one of the main components of basal laminae. It is elaborated by most cells, especially epithelial ones. It enables interactions between cells and the matrix.

2. Entactin: A sulfated glycoprotein that forms part of basal laminae. It is elaborated by most cells, especially epithelial ones. It has binding sites for laminin and type IV collagen, acting as a linking protein.

3. Tenascin: A non-fibrillar polypeptide glycoprotein formed by six chains. Structurally, it resembles a spider whose legs project radially. It is specifically expressed in embryonic tissues. It is involved in cell adhesion and is important in cell migration.

d.) Other Substances

Water, ions and mineral salts, plasma proteins, catabolism products and vitamin C.

Specialized Extracellular Matrix: Basal Lamina

• Concept: A specialized, thin layer of extracellular matrix, synthesized by cells associated with it. It supports stem cells, epithelial cells, muscle cells, Schwann cells and adipocytes, and separates them from adjacent connective tissue. It is the first mode of interface between these cells and the stroma of parenchymatous organs.
• Composition: Type IV collagen, fibronectin, proteoglycans and structural glycoproteins.

Molecular Structure

Type IV collagen forms sheets stacked in polygonal networks, which form the structural framework of the lamina.

Microscopic Structure

Under the light microscope it appears as a homogeneous band. Under the electron microscope it is a dense, electron-dense layer. With special techniques such as argyrophilic silver impregnation, it can be seen as a fine line, and it is recognized as the basement membrane.

Functions

Adhesion between cells and the stroma of parenchymatous organs, molecular filtration, control and organization of differentiation, and mutual interaction between cells through receptors and cell surface molecules of the matrix.

Cell Adhesion to the Matrix

It is produced through:

• Hemidesmosomes: Anchor the cytoskeleton of intermediate filaments to the basal lamina.
• Integrins: Transmembrane proteins that act as receptors. There are many types, and they interact with the matrix. They are heterodimers composed of alpha and beta glycoprotein chains. Their amino-terminal ends bind to the matrix.
• Glycoproteins that are not integrins: Generally bind to collagen fibers and other components.

Connective Tissue: Variety, Organization and Common Disorders

Composition:

1. Cells: Mesenchymal cells, fibroblasts, adipocytes, in transit or migrating cells.
2. Fibers: Collagen, elastic and reticular fibers.
3. Amorphous fundamental substance.
4. Interstitial fluid.

Types and distribution: Connective tissue varies in its components and is classified into six types:

• Mesenchymal: Found in the embryo, it is formed by mesenchymal cells, a network of cytoplasmic processes, a scarce amount of fibers and a relatively abundant fundamental substance.
• Mucous: Found in the umbilical cord, placental villi and young dental pulp. It has a gelatinous consistency, with scarce cells and a predominantly amorphous fundamental substance.
• Loose or areolar: Connective tissue with well-represented and harmonious components. It is the most widespread, and it contains abundant blood vessels and adipocytes in some areas.
• Elastic: Predominantly elastic fibers. Found in the ligamentum flavum of the vertebral column, the middle layer of the aorta and arteries, the elastic lamina of arteries and arterioles, the suspensory ligament of the penis and the vocal ligaments.
• Reticular: Reticular fibers formed by reticular cells, which belong to fibroblastic, histiocytic and primitive dendritic antigen-presenting cell lineages. It forms the supporting framework of the liver, bone marrow, hematopoietic tissue and lymphoid organs.
• Dense: Distinguished by a predominant fibrillar component and a relatively scarce amount of cells and fundamental amorphous substance. It forms part of tendons, ligaments, various organ capsules, fasciae of various organs, muscle fasciae, dura mater and the deep stroma of the cornea. Two subvariants are distinguished: ordered or organized, for example tendons and corneal stroma; and disordered or unorganized, for example the deep dermis.