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EXTRACELLULAR
MATRIX
PRESENTED BY
MUKESH SAH
RAM KUMAR SAH
ROSHAN YADAV
HERUNI
EXTRACELLULAR MATRIX
The extracellular matrix (ECM) is the noncellular component present within all tissues and organs, and provides not only essential physicalscaffolding for the cellular constituents but also initiates crucial biochemical and biomechanical cues that are required for tissue morphogenesis, differentiation and homeostasis
Cell adhesion to the ECM is mediated by ECM receptors, such as integrins, discoidin domain receptors and syndecans
the ECMdirects essential morphological organizationand physiological function by binding growthfactors (GFs) and interacting with cell-surfacereceptors to elicit signal transduction andregulate gene transcription.
• Provides support anchorage and for cells.
• Regulates and determine cells dynamic behaviour :- polarity of cells- cell differentiation- adhesion- migration
• Provides mechanical support for tissues and organ architecture.
- growth- regenerative and healing processes - determination and maintenance of the
structure• Place for active exchange of different metabolites, ions, water.
Function of ECM
The ECM of animal cells
• Animals cells lack
the structure and
support that a cell
wall provides
• Have an ECM
instead that
provides some of
the same support
Components of the ECM
• Cells secrete
glycoproteins
– This is the main
component of the
ECM
All 3 of these
are common
ECM
glycoproteins
Proteoglycans Proteoglycans represent a special class of glycoproteins that are heavily glycosylated (95%).
They consisit of core protein with one or more attached glycosamino glycan chain(s).
Function of Proteoglycans• organize water molecules
- resistant to compression
- return to original shape- repel negative molecules
• occupy space between cells and collagen• high viscosity
- lubricating fluid in the joints
• specific binding to other macromolecules• link to collagen fibers
- form network
- in bone combine with calciumsalts (calcium carbonate,hydroxyapatite)
• cell migration and adhesion- passageways between cells
• anchoring cells to matrix fibers
• Collagen is the most common glycoprotein
in the ECM
• Proteoglycans (a
glycoprotein) form
a woven network
outside cells
• Collagen are like
strong fibers that
run throughout
this network
• The most abundant protein in the body, making 25%-35% of all the whole-body proteins.
• Collagen contributes to the stability of tissues and organs.
• It maintains their structural integrity.
• It has great tensile strenght.
• The main component of fascia, cartilage, ligaments, tendons, bone and skin.
• Plays an important role in cell differentiation, polarity, movement
• Plays an important role in tissue and organ development
Collagen
Collagen is insoluble glycoprotein (protein + carbohydrate)
Collagen polypeptide structure:
- G – X – A – G – A – A – G – Y – A – G – A – A – G – X – A – G – A –
– A – G – X – A – G – A – A – G – Y – A – G – A – A – G – X – A – G –– A – A – G – X – A – G – A – A – G – Y – A – G – A – A – G – X – A –
G - glycine, X - proline or hydroxyproline, Y – lysin or hydroxylysine, A – amino acid
• Proline and hydroxyproline constitute about 1/6 of the total sequence, provide the stifness of the polypeptide chain.
• Carbohydrates : glucose, galactose
Collagen structure
Diversity of CollagensType I fibrils Skin, tendon, bone, ligaments, dentin, interstitium
Type II Fibrils Cartilage, vitreous humor
Type III Fibrils Skin, muscle, bv
Type IV 2D sheets All basement membranes
Type V Fibrils with globular
end
Cornea, teeth, bone, placenta, skin, smooth
muscle
Type VI Fibril-assoc. (I) Most interstitial tissues
Type VII Long anchoring fibril Skin--connects epidermal basement
membrane/hemidesmosome to dermis
Type IX Fibril-assoc. (II) Cartilage, vitreous humor
Type XIII Transmembrane Hemidesmosomes in skin
Type XV HSPG Widespread; near basement membranes in
muscle
Type XVII Transmembrane Hemidesmosomes in skin (aka BPAG2 or BP180)
• Elastin is a major protein component of tissues that require elasticity such as arteries, lungs, bladder, skin and elastic ligaments and cartilage.
• It is composed of soluble tropoelastinprotein containing primarily, glycine and valine and modified alanine and prolineresidues.
• Tropoelastin is a ~65kDa protein that is highly cross-linked to form an insoluble complex.
• The most common interchain cross-link in elastins is the result of the conversion of the amine groups of lysine to reactive aldehydes by lysyl oxidase. This results in the spontaneous formation of desmosine cross-links.
Elastin
• Cells are attached to
the ECM by another
glycoprotein:
fibronectin
• On one side,
fibronectin is attached
to proteins in the
plasma membrane
• On the other side, the
fibronectin is attached
to the glycoproteins of
the ECM
The ECM allows for cell to cell
communication
Intercellular junctions
• Cells in plants and animals are organized
into tissues, organs, and organ systems
• Cells in a tissue may adhere to each other
The Plasmodesmata of plants
• Cells walls of plants
are perforated with
small channels called
plasmodesmata
• Cytosol passes
through the channel,
thereby connecting
the two cells
• Water, solutes, even proteins and RNA can move between cells
• Allows plant cells to function as a unified system, rather than isolated cells
Intercellular Junctions in Animal
Cells
• 3 main types of junctions between animal cells
• These junctions are most common in epithelial tissue(skin, linings of organs, etc)
Tight junctions in animal cells
• The plasma
membranes of
neighboring cells are
very tightly pressed
together and bound
by proteins
• Forms a seal or
barrier around a group
of cells
Desmosomes or anchoring
junctions in animal cells
• Like rivets that fasten cells together in strong sheets
• Keratin filaments anchor these attachments in the cytoplasm
Gap junctions (or communicating
junctions) in animal cells
• Similar to plasmodesmata in plant cells
• Provides a channel between cells that cytosol can travel through
• Allows for cell to cell communication– Important in cardiac
tissue and embryonic tissue
The role and location of each of the 3 types of intercellular junctions
What binds the cells to the ECM?
Integrins
• Groups of transmembrane proteins
• Link cytoskeleton to ECM
• Fibronectinreceptor is best known
Scurvy
• Liver spots on skin, spongy
gums, bleeding from mucous
membranes, depression,
immobility
• Vitamin C deficiency
• Ascorbate is required for prolyl
hydroxylase and lysyl
hydroxylase activities
• Acquired disease of fibrillar
collagen
Some Genetic Diseases of Collagen
• Collagen I– Osteogenesis imperfecta
– Ehlers-Danlos syndrome type VII
• Collagen II– Multiple diseases of cartilage
• Collagen III– Ehlers-Danlos syndrome type IV
• Collagen IV– Alport syndrome, stroke, hemorrhage, porencephaly
• Collagen VII– Dystrophic epidermolysis bullosa (skin blistering)
Emphysema
• Damage to the lung air sacs (alveoli) that affects breathing
• Macrophages induced to “ingest”particles in smoke also secrete proteases that degrade elastic fibers
• Loss of lung elasticity makes exhalation difficult
• Increased alveolar size reduces the surface area for gas exchange
JOURNAL WORK USE OF ECM
By Anthony Catalano
The Extracellular Matrix (ECM) Provides support to
tissue
Composed of fibers: Collagen and Elastin
Made up of cells called Fibroblasts
Found in intercellular cavities
Discovery of ECM as a “Bioscaffold” 1989- Dr. Stephen
Badylak performed Aortic surgery (Cardiomyoplasty) on a canine
Replaced canine’s Aorta with a segment of the canine’s small intestine
Canine survived surgery and lived for another 8 years
Dr. Stephen Badylak
Further investigation of the ECM Dr. Stephen Badylak
determined it was the ECM that was the root cause of the successful surgery
Experimented on Xenogeneic ECM extracted from a pig bladder
Removed all cells from ECM
Performed same surgery with decellularized ECM
Physiology of Dr. Badylak’s Discovery The ECM contains cells
called fibroblasts When tissue becomes
damaged, fibroblasts secrete excess collagen to damaged site
The ECM scaffold prevents inflammation and excess collagen by promoting the secretion of growth factors
The growth factors prevent the immune system from secreting excess collagen and instead stimulates the body to repair tissue
Types of ECM scaffolding Today1.)Hydrated sheet ECM
3.)ECM Gel
(10ml-$175.88- Gibco®)
2.)Lyophilized powdered ECM(15mg-$400.00-CellAdhere™ )
Advantages and Disadvantages of ECM scaffoldingPROS
Biocompatibility
No immune (post-surgery) drugs required
Regain of tissue function
Regeneration of tissue without use of controversial harvesting of stem cells
CONS
Dependant on percentage of lost or damaged tissue (%25-80% max)
External Scarring
Recovery Rate (1-2 months)
Current Use of ECM scaffolds FDA approved for clinical
use in 1999
Dr. Stephen Badylak is working with wounded veterans to replace lost muscle tissue
80 patient study, 5 patients treated, all successful in regaining muscle function
Average of 12-15% regain in muscle mass
Marine Sgt. Ron Strang
Corporal Isaias Hernandez
Future of ECM Scaffolding Use for hospitals and the
military
Portable regenerative medicine for use at home (Band-Aids)
Rebuilding limbs or other artificial body parts*
Quicker recovery rate
Lower Cost
References Badylak, Stephen, Dr. "The Extracellular Matrix as a Scaffold for Tissue Reconstruction." CELL &
DEVELOPMENTAL BIOLOGY (2002): Pgs:377-382 Web.
Piore, Adam. "Discover Magazine." The Healing Power from Within 7 July 2011: 68-88. Web. Valentin, J. E., J. S. Badylak, G. P. McCabe, and
S. F. Badylak. "Extracellular Matrix Bioscaffolds for Orthopaedic Applications. A Comparative Histologic Study." The Journal of Bone and Joint Surgery 88.12 (2006): 2673-686. Print.
"Extracellular Matrix." Wikipedia. Wikimedia Foundation, 16 Oct. 2012. Web. 17 Oct. 2012. <http://en.wikipedia.org/wiki/Extracellular_matrix>.
Badylak, S. "Xenogeneic Extracellular Matrix as a Scaffold for Tissue Reconstruction.“ Transplant Immunology 12.3-4 (2004): 367-77. Print.
Sell, Scott A., Patricia S. Wolfe, Koyal Garg, Jennifer M. McCool, Isaac A. Rodriguez, and Gary L. Bowlin. "The Use of Natural Polymers in Tissue Engineering: A Focus on ElectrospunExtracellular Matrix Analogues." Polymers 2.4 (2010): 522-53. Print.