Extracellllular matrix

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.