Extracellular Matrix: Structure, Function & Diseases

Extracellular matrix (ECM) refers to all endogenous substances that are located outside the cells in the intercellular space. ECM is highly important for the strength and shaping of tissues and as a carrier for blood and lymphatic vessels and nerve fibers. The intercellular space represents a complex collection of a wide variety of macromolecules that belong either to the liquid or gel-like ground substance or to the fibers.

What is the extracellular matrix?

All endogenous substances that are located outside the cells in the intercellular space are part of the extracellular matrix (ECM). The ECM is also referred to as extracellular matrix or intercellular substance. Basically, substances can be distinguished in the ECM, which either belong to the basic substance or can be attributed to various fibers. Depending on the task and tissue, the composition of the ECM varies greatly. The substances forming the group of fibers include a variety of collagenous, reticular and elastic fibers, each of which fulfills different tasks and forms its part of the ECM in a very different composition depending on the type of tissue. The amorphous ground substance of the ECM fills all residual spaces as a liquid or as a gel, depending on the structure of the intercellular space and the fiber portion of the ECM. The composition of the ground substance is also highly differentiated depending on the tasks. A large part of the DCM is formed from glycosaminoglycans, long-chain polysaccharides that are mostly bound to proteins in the form of proteoglycans, with the exception of hyaluronic acid. For example, they perform numerous tasks in the formation, degradation and remodeling of tissues. In this context, so-called adhesion proteins should also be mentioned, which, as part of the EZM, make contact with receptors of the cells in complex processes.

Anatomy and structure

The anatomical structure of the ECM is very heterogeneous and depends on the tasks that the ECM must perform in the corresponding body region. The fibrous part of the ECM is mainly composed of collagenous proteins, of which 27 are known, each of which differs in its protein composition and also varies in its physiological and mechanical properties. Essentially, collagens are characterized by their tensile strength. Collagen fibers with a diameter of 2 to 20 micrometers are composed of many, 130 nanometer thick, collagen fibrils. Also important are the reticular fibers, which form microscopic nets or grids to accommodate capillaries, nerve fibers, fat cells and smooth muscle cells. Unlike collagen fibers, which are resistant to tearing and cannot be stretched, elastic fibers, which are made of the protein elastin, have the unique property of reversible stretching. A large part of the basic substance is formed by glycosaminoglycans – mostly in the form of proteoglycans, glycans bound to proteins, whose main function is to create the necessary connections between individual proteins. For example, the cartilage substance of joints consists of glycosaminoglycans and glycoproteins. In contrast to collagens, the cartilage substance of the joint surfaces is not characterized by tensile strength, but by high compressive strength. The hyaluronic acid contained in ECM has an extremely high water-holding capacity and contributes decisively to the water balance of the tissues.

Function and tasks

The extracellular matrix not only performs physical functions in terms of tensile or compressive strength, but also intervenes in metabolic processes. Through a wide variety of collagenous fibers, the ECM takes primary responsibility for shaping organs, and it holds organs in their intended position in the body. Through other collagens, the ECM provides tensile strength to all tendons and ligaments and three-dimensional strength to bones. It also provides the compressive and wear resistance of the surface cartilages on the friction surfaces of the joints. However, tensile, compressive and shear strength are not the only tasks of the ECM; it is also responsible for ensuring the necessary elasticity in the tissues so that certain organs can increase and decrease their circumference as needed without irreversible damage. Another important task is the activation of the body’s own repair mechanisms through the release of cytokines, which have an influence on the proliferation and differentiation of cells.The ECM therefore maintains a stock of cytokines that can be activated as needed – for example, to repair injuries. Signal transduction is also one of the tasks of the extracellular matrix. This refers to the release of so-called secondary messenger substances, whose “message” reaches the cell interior via specialized receptors and activates the cell to behave in a certain way or to start certain metabolic processes. Likewise, the determination of polarity, i.e., the organization and orientation of cells into a basal and an apical end, belongs to the scope of the extracellular matrix.

Diseases

The almost incalculable variety of functions and tasks incumbent on the extracellular matrix already suggest that disease-related or disease-induced dysfunctions can occur with mild to severe effects. As causer and starting point of many chronic diseases up to malignant and life-threatening processes, disturbances of the basic regulation are assigned, which is organized by the ECM. Many processes of disease progression, which are related to the basic regulation of the ECM via the release of cytokines, are not yet sufficiently understood. In many cases, an overloading of basement membranes of the affected organs with proteins has been identified as the causative factor. For example, these processes play an important role in the development and progression of dilated cardiomyopathy, which is manifested by symptomatic cardiac enlargement with simultaneously impaired pump function. In addition to acquired dysfunctions of the ECM, genetically determined functional anomalies of the extracellular matrix are also known, which usually manifest themselves in a defective synthesis of certain collagens. The defective collagen synthesis leads to the respective known disease patterns in the affected organs, such as in the rare brittle bone disease (osteogenesis imperfecta). Due to a genetic anomaly, osteogenesis imperfecta supplies defective collagen for bone formation. As a result, the bones are extremely brittle and deformities of the bones and spine and other symptoms usually occur.