The extracellular matrix (ECM) is a complex mixture of proteins and polysaccharides located outside cells that provides structural and biochemical support to surrounding cells. It is secreted locally by resident cells and undergoes constant remodeling. The major components of extracellular matrix include collagen, elastin, fibronectin and proteoglycans.
Components of Extracellular Matrix
Collagen- Collagen is the most abundant protein in the Extracellular Matrix and forms strong fibrous structures that provide tensile strength and scaffolding for cells to reside in. There are over 20 types of collagen identified but types I, II, III are most prevalent.
Elastin- Elastin allows tissues to stretch and recoil through elastic fibers that withstand mechanical forces. This enables tissues like skin, lungs and blood vessels to extend and contract repeatedly.
Fibronectin- Fibronectin is a glycoprotein that binds collagen, fibrin and cells to support cell attachment, migration and differentiation during wound healing and development.
Proteoglycans- Proteoglycans like hyaluronic acid, decorin and versican regulate cell adhesion, division and migration through their hydrated gel-like extracellular environment and ability to bind growth factors.
Roles of Extracellular Matrix
provides physical scaffolding and structural support for cells and tissues
mediates cell-cell and cell-matrix interactions through integrin receptor binding
acts as a reservoir for growth factors and cytokines that regulate tissue repair, development and immunity
transmits force and mechanical signals between neighboring cells
regulates cell proliferation, migration and differentiation during development and disease
ECM in Development and Maintenance of Tissues
During embryonic development, the ECM composition changes dynamically as new tissues form and differentiate. It specifies positional cues that direct cell fate decisions through local biochemical and biomechanical signals. In the adult, it provides the proper microenvironment for homeostasis and repair of tissues after injury.
Some key roles of ECM include:
Bone – Collagens, elastin and proteoglycans allow bones to resist tensile and compressive forces through their mineralized structure. This provides rigidity to skeletal frames.
Muscle – Elastic fibers, collagens and glycoproteins within muscle ECM transmit contractile forces between myofibrils and allow repetitive stretching and contraction during movement.
Vasculature – Elastin within arteries and veins enables them to expand and recoil with each heartbeat, regulating blood flow and pressure. Endothelial basement membrane maintains vessel wall integrity.
Skin – Collagen fibrils layer the epidermis and dermis, providing tensile strength and elastic recoil to withstand abrasion and pressure. Fibronectin helps bind dermal fibroblasts during wound healing.
Lungs – Collagen and elastic fibers comprise the alveolar walls that must inflate and deflate over 60,000 times daily for gas exchange. ECM elasticity allows for repeated lung expansion.
Diseases Associated with Extracellular Matrix Abnormalities
Defects in ECM structure or function underlie many diseases:
– Connective tissue disorders like Marfan syndrome and Ehlers-Danlos syndrome arise from genetic defects in collagens and other matrix proteins, weakening tendons, blood vessels and joints.
– Skin aging is due to decreased collagen synthesis and increased breakdown by matrix metalloproteinases as we advance in age, causing wrinkles and sagging.
– Pulmonary fibrosis occurs when excess collagens accumulated amid lung tissue, stiffening walls and impairing oxygen exchange.
– Heart disease risk is elevated with abnormalities in elastic fiber deposition in arterial walls, predisposing to atherosclerosis.
– Cancer cell metastasis relies on secretion of proteinases to invade through basement membrane barriers and migrate to distant sites.
– Wound healing is impaired when matrix production or remodeling is dysregulated during inflammation and tissue regeneration phases.
Therapies Targeting Extracellular Matrix
Due to the central roles of ECM in health and disease, new therapies are targeting this compartment:
– Collagen supplements are used cosmetically or to treat osteoporosis and fibrosis by increasing structural proteins.
– Botulinum toxin injections block muscle ECM degradation in wrinkles by inhibiting metalloproteinases.
– Anti-fibrotic drugs inhibit collagen synthesis for lung diseases like idiopathic pulmonary fibrosis.
– Drugs preventing integrin-ECM interactions in cancer aim to block tumor cell migration and angiogenesis.
– Growth factor supplements promote wound healing by stimulating new ECM formation during injury repair.
ECM provides indispensable scaffolding and signals regulating tissue architecture and homeostasis. Understanding its composition and dynamic regulation promises to yield novel strategies for regenerative medicine, anti-aging and disease treatment.
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