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Lecture 15 Extracellular Matrix and Mechanical Signaling

Lecture 15 Extracellular Matrix and Mechanical Signaling -...

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IPHY 3060 Lecture 15: Extracellular Matrix and Mechanical Signaling
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The cytoskeleton supports cells from within
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The cytoskeleton supports cells from within But cells need to be supported from outside as well
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Extracellular Matrix: A complex meshwork of proteins and polysaccharides that supports cells and organizes tissues
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Functions of the Extracellular Matrix Protects and supports cells physically Acts as a barrier to substances outside the cell Binds to and modifies growth factors Transmits mechanical signals to and from the cells
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Examples of Extracellular Matrix Epithelial cells sit on a bed of ECM ECM
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Examples of Extracellular Matrix Each individual skeletal muscle fiber is surrounded by its own ECM
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3 Main Components of the ECM Collagens —proteins that provide strength and stiffness to ECM Proteoglycans —large molecules containing a peptide core surrounded by polysaccharide chains, provide cushion Multiadhesive proteins —link ECM proteins to cytoskeletal proteins—laminin, fibronectin, entactin
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Collagen Large family of proteins Provide mechanical strength Can be either fibrillar or sheet forming Fibrillar collagen Sheet collagen
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Proteoglycans Consist of a peptide core with long sugar chains coming off it Sugars attract water to form a gel Gel helps cushion cells
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Multiadhesive Proteins Large proteins that are usually heavily glycosylated Link ECM to cell surface proteins called adhesion receptors Bind to collagen and proteoglycans Examples: laminins, fibronectins
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ECM is produced by fibroblasts—special connective tissue cells found in all tissues
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Degradation of ECM proteins— matrix metalloproteinases Secreted by fibroblasts and all cells MMPs are proteases that specifically degrade ECM proteins —collagens, laminins, fibronectins
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Fibrosis
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Fibrosis: The excessive formation of extracellular matrix
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Fibrosis can be caused by 3 things: Increased fibroblast proliferation Increased ECM production by existing fibroblasts Decreased ECM degradation
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Fibrosis Is often a consequence of chronic diseases characterized by inflammation and increased growth factor and cytokine expression which promote increased fibroblast proliferation and/or ECM protein secretion
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Liver Fibrosis Replacement of healthy hepatocytes with connective tissue due to death of hepatocytes and over- production of ECM Liver becomes hardened—cirrhosis Major cause—chronic alcohol abuse
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Lung Fibrosis Lung becomes less elastic, makes breathing difficult Caused by exposure to toxins such as cigarette smoke particulates
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Lung Fibrosis
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