Lecture+21-23-ECM-1 - Extracellular Extracellular Matrix...

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Unformatted text preview: Extracellular Extracellular Matrix (ECM) ECM components components ECM synthesis and degradation ECM receptors Mechanical property of ECM Extracellular Matrix (ECM) Extracellular Matrix (ECM) • ECM is a molecular complex that has basic components collagens and other glycoproteins, hyaluronic acid, glycoproteins, hyaluronic acid, proteoglycans, glycosaminoglycans, and elastins. • ECM harbors molecules such as growth factors, cytokines, matrix-degrading enzymes, and their inhibitors. enzymes, and their inhibitors. Tissues are composed of cells Tissues are composed of cells and and extracellular Matrix (ECM) Examples of extremes: • Connective tissues: mostly ECM tissues: mostly ECM • Epithelial tissues: mostly cells Two Two main classes of macromolecules in ECM • Fibrous proteins • Structural: collagen, elastin, etc.(tensile) • Adhesive: fibronectin, laminin, etc. • Glycosaminoglycans and proteoglycans (highly negatively charged polysaccharide chains resist negatively charged polysaccharide chains, resist compressive force) • Hyaluronan • Chondroitin sulfate and dermantan sulfate • Heparin sulfate and heparin • Keratin sulfate Collagen Collagen • Collagen(s) is the most abundant protein, forming is the most abundant protein forming 1/3 of total protein content in the body. • ~ 20 different collagen genes have been identified. • Type I collagen accounts for over 80% of all collagen content. Present in all tissues. • Some collagens are tissue specific, e.g. – Type II found in cartilage, cornea – Type III present in proliferating tissues, thus more in fetal III present in proliferating tiss th more in fetal than in adult tissues, more in healing wounds – Type IV in basement membranes Collagens: Major proteins of ECM Collagens: Major proteins of ECM Elastin provides elasticity to tissues Elastin provides elasticity to tissues Tissue elasticity arises from unique polymeric protein elastin. Elastin occurs in close contact with collagen networks. Distribution and relative content of these two insoluble proteins these two insoluble proteins determine the function of many tissues, e.g. blood vessels, skin, tendons, ligaments. Elastin provides extensibility, collagen regulates the limits of extension extension. The Structure of Fibronectin Dimmer The Structure of Fibronectin Dimmer Molecular Molecular Interaction of Fibronectin with Adhesion Receptors An aggrecan aggregate from cartilage An aggrecan aggregate from cartilage Proteoglycans Proteoglycans Structure Structure of Basal Lamina Synthesis and Assembly of ECM Soluble matrix Regulators of matrix assembly Insoluble Polymeric matrix Cells Soluble growth and differentiation factors Matrix bound growth and diff differentiation factors Bioactive matrix Matrix Matrix Synthesis: Assembly of collagen fibrils Degradation of ECM Degradation of ECM • Matrix metalloproteinases (MMPs) Zinc dependant Secreted or membrane-associated • Tissue inhibitors of MMPs Receptors Receptors for ECM • Integrin family receptors: a family of heterodimeric transmembrane proteins composed of and subunits. • Non-integrin family receptors: e.g., cell surface proteoglycans Cell Integrins Focal Adhesion Extracellular matrix Nucleus The The structure of an integrin receptor (Ca2+, Mg2+) IntegrinsIntegrins-ECM binding Different Different cells may express different types of integrins • Osteoblasts: v, 1, 2, 3, 5, 1, 3 • Osteoclasts: v, 2, 3, 4, 5, 1, 3 • Chondrocytes: v, 2, 5, 6, 10, 1 Proteoglycan receptors • Syndecan (binds to hyaluronic acid collagens) • CD44 (binds to hyaluronic acid, collagens) • RHAMM (receptor for hyaluronate-mediated motility) Cell Cell-ECM Interactions Interactions • Force transduction: cytoskeleton and ECM transduction: cytoskeleton and ECM reorganization transduction • Signal transduction • Adhesion and migration • Proliferation and apoptosis and apoptosis • Differentiation Importance of Cytoskeleton in Cell Adhesion Im ECM modulates cytoskeleton structure ECM modulates cytoskeleton structure Cells exert contraction force on ECM Cells contraction force on ECM A B 1 cm C Role of focal adhesion kinase (FAK) Role of focal adhesion kinase (FAK) in integrinin integrin-mediated signaling Mechanical properties of ECM •Stress, strain and constitutive equation •Elastin, collagen and tissue (tendon) •Characteristics of soft tissue •Incremental laws and pseudo-elasticity •Viscoelastic models: dashpot and spring ...
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This note was uploaded on 01/21/2012 for the course BIOE 116 taught by Professor Various during the Fall '10 term at Berkeley.

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