The extracellular matrix (ECM) serves as the non-cellular framework within tissues, providing both structural and biochemical support to the cells it surrounds. This intricate network is not merely a passive scaffold but actively influences cellular functions. It is composed of macromolecules and minerals, including proteins and glycoproteins, that collectively maintain tissue integrity and function. The ECM’s characteristics determine the overall properties of a tissue, such as the rigidity of bone or the flexibility of cartilage.
The Ground Substance
The ground substance is a gelatinous material that fills the spaces between cells and protein fibers within the ECM. This component is primarily water, accounting for approximately 90% of the ECM’s composition, which is stabilized by large macromolecules that give it a viscous, gel-like consistency. This hydrated, porous gel allows for the diffusion of water-soluble molecules and cell movement while resisting compressive forces.
The ground substance consists mainly of glycosaminoglycans (GAGs), proteoglycans, and adhesive glycoproteins. GAGs are long, unbranched polysaccharide chains made of repeating disaccharide units, with hyaluronic acid being a prominent non-sulfated example. Other GAGs, such as chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate, are sulfated and found attached to proteins. These negatively charged GAGs attract positive ions, like sodium, drawing in water to form a hydrated gel that resists compression.
Proteoglycans are macromolecules formed when many GAG molecules attach to a core protein. For instance, aggrecan, found in cartilage, has a protein core bound to keratan sulfate and chondroitin sulfate. These structures are responsible for the gel-like properties and the ground substance’s ability to absorb significant amounts of water. Adhesive glycoproteins, such as fibronectin and laminin, reside in the ground substance, connecting ECM components to one another and to cell surfaces.
The Protein Fibers
Embedded within the ground substance are various protein fibers that provide strength and elasticity to connective tissues. These fibers vary in diameter and arrangement, influencing the mechanical properties of different tissues. While the ground substance excels at resisting compression, these fibers are adept at withstanding tensile forces.
Collagen fibers are the most abundant fibrous protein in the ECM, making up about 25% of total protein mass. Composed primarily of amino acids like glycine and proline, collagen molecules consist of three protein chains that wrap into a helical structure. Type I is the most common, accounting for 90% of all collagens and found extensively in bone, skin, tendons, and ligaments. Collagen is secreted by fibroblasts as procollagen, which then aggregates into strong, crosslinked fibrils and fibers in the extracellular space, providing substantial tensile strength.
Elastic fibers provide flexibility and the ability to recoil after stretching. These fibers are composed of the protein elastin, which is secreted as tropoelastin and then assembled into fibers on a scaffold of microfibrils. Elastin is prevalent in tissues requiring significant elasticity, such as blood vessels and skin. Elastic fibers are important for the tissue’s ability to stretch and recoil.
Reticular fibers are a type of collagen fiber, composed of Type III collagen. These thin, branching fibers form networks that provide a supportive framework for soft tissues and organs, such as lymph nodes, spleen, and bone marrow. They are often found at the boundary of connective tissue and other tissues, offering a mesh-like support structure.
Functions of the Extracellular Matrix
The ECM performs several important functions for tissue organization and cellular behavior. It provides mechanical support, acting as a scaffold that positions cells and helps determine the shape and properties of tissues. Without the ECM, tissues like bone would lack rigidity, and organs like the lungs would lack their characteristic flexibility.
Beyond structural support, the ECM mediates cell adhesion and migration. Cells interact with the ECM through receptors, such as integrins, which link the ECM to the cell’s internal cytoskeleton. These interactions are important for regulating cell behavior, including cell attachment and movement within tissues. It also facilitates cell-to-cell communication, allowing cells to receive signals from their environment.
The ECM also functions as a reservoir for growth factors and signaling molecules. These molecules can bind to ECM components and be released in response to specific signals, influencing cell growth, differentiation, and proliferation. This interaction makes the ECM a participant in processes like wound healing, providing a scaffold for cell adhesion and migration during tissue repair.
How ECM Varies Across Tissues
The composition and organization of the extracellular matrix differ among connective tissues, directly influencing their properties and functions. The proportions and types of ground substance components and protein fibers are tailored to meet the mechanical and biological demands of each tissue.
For instance, bone tissue has a rigid, mineralized ECM, where Type I collagen fibers are mixed with a matrix of calcium phosphate crystals, which can constitute up to 70% of its dry weight. This mineralization provides bone with its stiffness and hardness, while collagen allows for some elasticity to prevent fragility. In contrast, cartilage, found in joints, has a flexible and resilient ECM composed of Type II collagen and a concentration of glycosaminoglycans like hyaluronan and aggrecan, helping it withstand compressive forces.
Loose connective tissue, often found under epithelia, has a large amount of ground substance and fewer fibers, creating an open structure allowing for diffusion of nutrients and waste. Tendons, which connect muscles to bones, have an ECM made of Type I collagen, with fibers arranged in parallel to provide tensile strength along one axis. Adipose tissue, for energy storage, features a loosely organized ECM with many cells. Blood is considered a fluid connective tissue, with plasma serving as its fluid ECM, suspending cells for circulation.