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Lecture 16 Cell Biolgy ٢٢٢ ١ Extracellular Matrix 1) 2) Materials that are external to the plasma membrane composed of 2 major materials : Glycosoaminoglycans (GAG) Fbrillar proteins. Glycosoaminoglycans Large unbranched, polysaccharides chains composed of repeated disaccharide units. These polysaccharides Link to backbone of proteins forming proteoglycans. They are 4 groups according to structure : hyaluronic Acid, chondroitin sulfate, dermatan sulfate, heparin Sulfate and heparin, keratan sulfate. Cell Biolgy ٢٢٢ ٢ Properties of GAG 1- A high negative charge because one of the repeated units is Nacetylglucosamine or N-cetyl galactosamine is sulfated (SO3-), and most GAG has a second sugar uronic acid with a COO group. 2) Strongly hydrophilic behavior. 3) Retension of +ve ions (e.g.Na+) and water. 4) Covalent attachment with proteins to form proteoglycans Fibrillar proteins They are collagen, fibrillin, elastin, fibronectin. Role : 1) Provide different tensile properties to support tissues 2) Anchoring for other cellular elements in tissues. Cell Biolgy ٢٢٢ ٣ Glycosaminoglycans Distribution Hyaluronic acid Cartilage, synovial fluid, Skin. Chondroitin sulfate Cartilage, bone, skin Dermatan sulfate Skin, blood vessels, heart Heparan sulfate Basement membrane, lung arteries. Heparin Lung, liver, skin, mast cell granules. Keratan sulfate Cartilage, vertebral discs Cell Biolgy ٢٢٢ ٤ 1) Collagen - Collagen are a family of closely related proteins which can aggregrate to produce either filaments, fibrils or meshwork, they interact with other proteins to provide support for ECM Are 20 types of polypeptide chains (α-chains) produced by different genes and wound together to form triple helix structure. Produced by fibroblasts. After proteolytic cleavage, the triple helical portions are assembled into long filaments and bundles. 2) Elastin -Is a protein assembled into filaments and sheets. Elastic fibers are formed by interaction between elastin and fibrillin (the latter organize secreted elastin to form elastic fibers. 3) Fibrillin -Fibrils forming glycoproteins (microfibrils). Main component of ECM. -Microfibrils are one constituent of elastic fibers + suspensory fibers of lens. Microfibrils are prominent in elastic containing extracellular matrix particullary in lung, skin and blood vessels. Cell Biolgy ٢٢٢ ٥ Cell Biolgy ٢٢٢ ٦ 4) Fibronectin 4) Fibronectin -Is a multifunctional glycoprotein an has to adhere to different tissue components because it possesses binding sites that bind collagen as well as cell adhesion molecules. Most cells have cell surface receptors for fibronectin called integrins. 5) Integrins -Transmembrane proteins similar to cell membrane receptors in that they form bonds with ligands. Ligands are not signaling molecules but structural members of ECM such as collagen, laminin and fibronectin. Integrins have 3 domains: a binding domain to actin, a transmembrane domain and an extracellular domain binding to fibronectin. Transmit information between extracellular and cytoskeleton, thus integrating changes occuring inside and outside cell. Cell Biolgy ٢٢٢ ٧ Cell Biolgy ٢٢٢ ٨ Muscle Cell Biolgy ٢٢٢ ٩ Muscle Muscle is the body's contractile tissue. ‘Contraction’, in the physiological sense, may involve shortening and change of shape, or it may generate force without any change in length. All contraction depends on physicochemical alterations in the molecules of protein filaments within the cells, resulting in the generation of force at linkages (cross-bridges) between two different kinds of filament. The main proteins involved, in the respective filaments of all types of muscle, are actin and myosin; and in all muscles the process is powered by breakdown of ATP, during which chemical energy is converted by the interactions between these proteins into the mechanical energy of contraction. To initiate the process, muscle cells require excitation, which leads to contraction by a sequence that involves an increase in the concentration of free calcium ions inside the cell — a sequence termed excitation- contraction coupling. Cell Biolgy ٢٢٢ ١٠ Muscle types There are three types of muscle: Skeletal muscle or "voluntary muscle" is anchored by tendons to bone and is used to effect skeletal movement such as locomotion and in maintaining posture. An average adult male is made up of 42% of skeletal muscle and an average adult female is made up of 36% (as a percentage of body mass). Smooth muscle or "involuntary muscle" is found within the walls of organs and structures such as the esophagus, stomach, intestines, bronchi, uterus, urethra, bladder, blood vessels, and the arrector pili in the skin (in which it controls erection of body hair). Unlike skeletal muscle, smooth muscle is not under conscious control. Cardiac muscle is also an "involuntary muscle" but is more akin in structure to skeletal muscle, and is found only in the heart. Cell Biolgy ٢٢٢ ١١ Muscle types Cell Biolgy ٢٢٢ Cardiac and skeletal muscles are "striated" in that they contain sarcomeres and are packed into highly-regular arrangements of bundles; smooth muscle has neither. While skeletal muscles are arranged in regular, parallel bundles, cardiac muscle connects at branching, irregular angles (called intercalated discs). ١٢ Skeletal muscle Striated muscle contracts and relaxes in short, intense bursts, whereas smooth muscle sustains longer or even near-permanent contractions. Skeletal muscle is made up of individual components known as muscle fibers. These fibers are formed from the fusion of developmental myoblasts. The myofibers are long, cylindrical, multinucleated cells composed of actin and myosin myofibrils repeated as a sarcomere, the basic functional unit of the cell and responsible for skeletal muscle's striated appearance and forming the basic machinery necessary for muscle contraction. The term muscle refers to multiple bundles of muscle fibers held together by connective tissue. Cell Biolgy ٢٢٢ ١٣ Sarcomere A sarcomere is the basic unit of a muscle's cross-striated myofibril. Sarcomeres are multi-protein complexes composed of three different filament systems. The thick filament system is composed of Myosin protein which is connected from the M-line to the Z-disc by titin. It also contains myosin-binding protein C which binds at one end to the thick filament and the other to Actin. The thin filaments are assembled by Actin monomers bound to nebulin, which also involves tropomyosin (a dimer which coils itself around the F-actin core of the thin filament). Nebulin and titin give stability and structure to the sarcomere. A muscle cell from a biceps may contain 100,000 sarcomeres. Cell Biolgy ٢٢٢ ١٤ Cell Biolgy ٢٢٢ ١٥ Calcium pump Cell Biolgy ٢٢٢ There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into cells, yet it is very important for cells to maintain low concentrations of Ca2+ for proper cell signalling; thus it is necessary for the cell to employ ion pumps to remove the Ca2+. An ion pump is a type of vacuum pump capable of reaching up to 10-11 under ideal conditions ١٦ How motor neurones stimulate muscle contraction Signals from central nerves system (CNS) conveyed by motor neurons send an action potential. Axon terminal release neurotransmitter acetylcholine which diffuses across the synapse to plasma membrane of muscles fibres. Plasma membranes of muscles. fibres have 2 ways : 1) Electrically exitable ( propagation of action potential). 2) plasma membrane extends to the interior by in foldings called Transverse tubules called T tubules. When a motor neuron triggers an action potential , it spreads to entire volume of cell not only to surface. T tubules are in close contact with ER( interconnected tubules within muscles. fibres). Cell Biolgy ٢٢٢ ١٧ Cell Biolgy ٢٢٢ ١٨ Muscle contraction Action potential cause channels to open and release Ca2+ into cytoplasmic fluid. Function of Ca2+ : 2 regulatory proteins block myosin binding sites are; troponin and tropomyosin. muscles. fibres cannot contract while these sites are blocked. Ca2+ binds to troponin to moves tropomyosin away from myosin binding sites allows contraction to occur. As long as cytoplasmic fluid contains enough Ca2+ contraction continue. when motor neuron stop sending action potential ER pumps Ca2+ back out of cytoplasmic fluid. Binding sites on actin filaments are again blocked. Cell Biolgy ٢٢٢ ١٩ Cell Biolgy ٢٢٢ ٢٠ Cell Biolgy ٢٢٢ ٢١ Cell Biolgy ٢٢٢ ٢٢ Cell Biolgy ٢٢٢ ٢٣ Cell Biolgy ٢٢٢ ٢٤