Lecture 13 - The ECM (Compositions and Functions)

13. The Extracellular Matrix (ECM): Composi on and Func ons Introduc on The extracellular matrix (ECM) is a complex network of proteins, glycoproteins, and polysaccharides that offers structural and biochemical guide to cells inside ssues. The ECM performs a essen al func on in maintaining ssue architecture, regula ng cell behavior, and facilita ng conversa on among cells. It is vital for strategies together with wound recovery, improvement, and ssue repair. Composi on of the Extracellular Matrix The ECM consists of numerous molecules, every contribu ng to its structure and characteris c: • Collagen: o Collagen is the most ample protein inside the ECM and affords tensile electricity to ssues. There are several types of collagen, every with unique roles in one-of-a-kind ssues. O Type I collagen is the maximum not unusual and is determined in pores and skin, tendons, and bones. Type II collagen is determined in car lage, whilst Type III collagen is present in re cular fibers of the pores and skin, blood vessels, and internal organs. • o Elas n: Elas n is a incredibly elas c protein that allows ssues to stretch and recoil. It is ample in ssues that require elas city, which include the pores and skin, lungs, and blood vessels. O Elas n fibers are interwoven with collagen fibers, supplying both strength and versa lity to the ECM. • Glycoproteins: o Glycoproteins are proteins with connected carbohydrate chains that play a posi on in cellular adhesion and communique. Key glycoproteins within the ECM consist of:  Fibronec n: Involved in mobile adhesion, migra on, and wound restora on.  Laminin: A predominant component of the basal lamina, laminin performs a posi on in cellular adhesion, differen a on, and ssue employer.  Integrins: Transmembrane receptors that mediate cellular-ECM interac ons, integrins join the ECM to the cytoskeleton and are concerned in signal transduc on. • Proteoglycans: o Proteoglycans are proteins with connected glycosaminoglycan (GAG) chains, that are long, unbranched polysaccharides. Proteoglycans make contribu ons to the ECM's hydra on, resistance to compression, and poten al to bind signaling molecules. O Hyaluronic Acid: A huge GAG that paperwork a gel-like matrix, offering lubrica on and hydra on to ssues. O Chondroi n Sulfate: A GAG observed in car lage, contribu ng to its resilience and resistance to compression. • Basal Lamina: o The basal lamina is a specialized layer of the ECM that underlies epithelial cells and surrounds muscle, nerve, and fat cells. It is composed of collagen IV, laminin, and other ECM components, supplying structural help and regula ng cell behavior. Func ons of the Extracellular Matrix The ECM performs several cri cal func ons which can be important for ssue homeostasis and cellular feature: • Structural Support: o The ECM affords structural support to ssues, keeping their form and integrity. It acts as a scaffold that holds cells in area and organizes them into useful units. • Cell Adhesion and Migra on: o The ECM mediates mobile adhesion through interac ons between cellular surface receptors (which includes integrins) and ECM components. This adhesion is crucial for cell migra on, ssue restore, and embryonic improvement. • Regula on of Cell Behavior: o The ECM regulates cell behavior by way of impar ng biochemical cues that influence cellular differen a on, prolifera on, and survival. These cues are o en mediated by signalling molecules, which include boom elements, which might be sure to ECM components. • Wound Healing and Tissue Repair: o During wound recovery, the ECM affords a scaffold for the migra on and prolifera on of cells involved in ssue restore. The ECM is ac vely remodelled at some stage in this system, with the deposi on of new ECM components and the breakdown of damaged ones. • Barrier Func on: o The ECM acts as a barrier that regulates the movement of cells and molecules within ssues. The basal lamina, as an instance, paperwork a selec ve barrier that controls the exchange of molecules among the epithelium and underlying connec ve ssue. • Storage and Release of Signaling Molecules: o The ECM shops and regulates the provision of signaling molecules, together with growth factors and cytokines. These molecules are launched in reac on to par cular indicators, influencing cellular behavior and ssue responses. ECM Remodeling The ECM is constantly being remodeled through the synthesis and degrada on of its addi ves: • o Matrix Metalloproteinases (MMPs): MMPs are a own family of enzymes that degrade ECM components, taking into account ssue reworking and repair. MMP pas me is ghtly regulated to preserve ECM integrity and prevent immoderate degrada on. • Tissue Inhibitors of Metalloproteinases (TIMPs): o TIMPs are proteins that inhibit MMP interest, ensuring a stability among ECM synthesis and degrada on. Dysregula on of this stability can lead to sicknesses which includes fibrosis and most cancers. ECM in Disease Altera ons in ECM composi on or characteris c can contribute to numerous diseases: • Fibrosis: o Excessive deposi on of ECM components, specifically collagen, can lead to fibrosis, a situa on characterised by means of the thickening and s ffening of ssues. Fibrosis can occur in organs consis ng of the liver, lungs, and coronary heart, leading to impaired feature. • Cancer: o The ECM performs a role in most cancers progression with the aid of influencing tumor mobile conduct and the tumor microenvironment. Cancer cells can remodel the ECM to sell invasion, metastasis, and resistance to therapy. • Osteoarthri s: o In osteoarthri s, the degrada on of ECM components in car lage leads to the lack of joint func on and ache. The balance between ECM synthesis and degrada on is disrupted, resul ng inside the breakdown of car lage. • Gene c Disorders: o Muta ons in genes encoding ECM components can lead to gene c problems, which includes Marfan syndrome, characterised through defects in elas n fibers, or Ehlers-Danlos syndrome, affec ng collagen synthesis and leading to hyperelas c skin and joint instability.