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Lecture 16
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Extracellular Matrix
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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.
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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.
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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
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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.
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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.
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Muscle
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Muscle
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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.
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Muscle types
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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.
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Muscle types
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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).
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Skeletal muscle
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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.
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Sarcomere
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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.
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Calcium pump
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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
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How motor neurones stimulate muscle
contraction
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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).
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Muscle contraction
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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.
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