extra cellular matrix

8/8/2019 Extra Cellular Matrix

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Most of the cells in multicellular organisms are organized intoMost of the cells in multicellular organisms are organized intocooperative assembliescooperative assemblies -- tissuestissues, which are in turn associated in, which are in turn associated in

various combinations as larger functional units calledvarious combinations as larger functional units called organsorgans..

The cells in tissues are in direct contact with neighboring cellsThe cells in tissues are in direct contact with neighboring cellsand very often they are linked to each other at specializedand very often they are linked to each other at specializedintercellular junctionsintercellular junctions..

Some part of the cell is usually in contact with a complexSome part of the cell is usually in contact with a complexnetwork of secreted extracellular macromolecules, called thenetwork of secreted extracellular macromolecules, called theextracellular matrixextracellular matrix....

This matrix helps to hold cells and tissues together, and itThis matrix helps to hold cells and tissues together, and it provides an organized lattice within which cells can migrate and provides an organized lattice within which cells can migrate andinteract with one another.interact with one another.

DR.WAEL ELFARESIDR.WAEL ELFARESI 11



Cell AdhesionsCell Adhesions--Cell Cell Cell surface molecule protein:Cell surface molecule protein: IntegrinIntegrin

Binds and mechanically fixes cells to ECMBinds and mechanically fixes cells to ECM Serves in signal transduction alsoServes in signal transduction also

At focal adhesionAt focal adhesion ----> it is part of the Focal Adhesion> it is part of the Focal Adhesion KinaseKinase

PathwayPathway

triggers cell anchoringtriggers cell anchoring

Cell adhesion molecules:Cell adhesion molecules: CAM's; usuallyCAM's; usually glycoproteins glycoproteins

CadherensCadherens: calcium dependent: calcium dependent

important in initial attachment such as in development of cells,important in initial attachment such as in development of cells,

maintaining the structure and integrity of cellsmaintaining the structure and integrity of cells

SelectinsSelectins

IgIg superfamilysuperfamily

N N -- CAM's, nerve cells and calcium independentCAM's, nerve cells and calcium independentDR.WAEL ELFARESIDR.WAEL ELFARESI 22



Cells are joined by a varietyCells are joined by a variety

of intracellular junctionsof intracellular junctions

Cells are joined by a varietyCells are joined by a variety

of intracellular junctionsof intracellular junctions

In multicellular organisms, adajcent cells are held together by several types of specialized junctions . ± Tight junctions (found in animals): specialized

"belts" that bind two cells tightly to each other,

prevent fluid from leaking into intracellular space.

± Desmosomes (found in animals): intercellular "rivets" that create tight bonds between cells, but allow fluids to pass throughintracellular spaces.

± Gap junctions (found in animals): for med by two connecting protein rings embedded in cell membrane of ad jacent cells. Allows passage of water, small solutes, but not macromolecules (proteins, nucleic acids).

± Plasmodesmata (found in plants): channels connecting cells; allow free passage of water and small solutes, but not macromolecules (proteins, nucleic acids).

DR.WAEL ELFARESI 3



In biology, extracellular matrix (ECM)

is any material part of a tissue that is

not part of any cell.

Most of the cells inMost of the cells in multicellularmulticellular

organisms are surrounded by aorganisms are surrounded by a

complex mixture of nonliving materialcomplex mixture of nonliving materialthat makes up the extracellular matrixthat makes up the extracellular matrix

(ECM).(ECM).




MostMost normalnormal vertebratevertebrate cellscells cannotcannot survivesurviveunlessunless theythey areare anchoredanchored toto thethe

extracellular extracellular matrixmatrix.. ThisThis anchorageanchorage

dependencedependence isis oftenoften lostlost whenwhen aa cellcellturnsturns cancerouscancerous..

For For example,example, ((HeLaHeLa cellscells,, areare amongamong thethe

fewfew typestypes of of vertebratevertebrate cellcell thatthat cancan be begrowngrown inin liquidliquid cultureculture..))




functions of The ECMfunctions of The ECM

Given this diversity, it can serve many number of Given this diversity, it can serve many number of functions.functions.

1.1. providing support and anchorage for the cells. providing support and anchorage for the cells.

2.2. The ECM functions in a cell's dynamic behavior.The ECM functions in a cell's dynamic behavior.3.3. TheThe integrinsintegrins transmit mechanical stimuli fromtransmit mechanical stimuli from

the ECM to the cytoskeleton.the ECM to the cytoskeleton.

4.4. Many cells bind to components of theMany cells bind to components of the

extracellular matrix. This cellextracellular matrix. This cell--toto--ECMECM adhesionadhesionis due to specific cell surface adhesion proteinsis due to specific cell surface adhesion proteinsknown asknown as cellular adhesion moleculescellular adhesion molecules (CAM).(CAM).




ECM contains many components:

proteins such as fibrin and elastin, minerals such as hydroxylapatite (the case of bone)the case of bone)

fluids such as blood plasma or serum with secreted

free flowing antigens.

ECM's main component is various glycoproteins.

In most animals, the most abundant glycoprotein inthe ECM is collagen.




In plants,In plants,

the ECM is primarily composed of the ECM is primarily composed of cellulosecellulose..

InIn arthropodsarthropods andand fungifungi,,

the ECM is largely composed of the ECM is largely composed of chitinchitin..

Extracellular matrix is the defining feature of connective tissue.




Connecting Cells to the ECMConnecting Cells to the ECM Cells attach to the ECM by means of Cells attach to the ECM by means of

transmembranetransmembrane glycoproteinsglycoproteins calledcalled integrinsintegrins..

The extracellular portion of The extracellular portion of integrinsintegrins binds to binds to

various types of ECM proteins: various types of ECM proteins: collagens collagens

lamininslaminins

fibronectin fibronectin

The intracellular portion binds to the The intracellular portion binds to the actinactinfilamentsfilaments of the of the cytoskeletoncytoskeleton..




In some cases cells are attached to the matrixIn some cases cells are attached to the matrixat specialized regions of their plasmaat specialized regions of their plasmamembrane calledmembrane called cellcell--matrix junctions.matrix junctions.

Two extreme examplesTwo extreme examples::

Connective tissuesConnective tissues -- extracellular matrix is plentiful and cellsextracellular matrix is plentiful and cellsare sparsely distributed within it.are sparsely distributed within it. The matrix,The matrix, rather than therather than thecells, bears most of the stressescells, bears most of the stresses to which the tissue isto which the tissue issubjected.( bone)subjected.( bone)

Epithelial tissuesEpithelial tissues -- cells are tightly bound together into sheets;cells are tightly bound together into sheets;

extracellular matrix is scanty.extracellular matrix is scanty. The cells themselves bear mostThe cells themselves bear mostof the stressesof the stresses by means of strong intracellular protein by means of strong intracellular proteinfilaments thatfilaments that crisscriss--cross through the cytoplasm of each cellcross through the cytoplasm of each celland bind to specialized cell junctions.and bind to specialized cell junctions.




The macromolecules that The macromolecules that constitute theconstitute the

extracellular matrix extracellular matrix

are mainly secretedare mainly secreted

locally by cells in thelocally by cells in the

matrix matrix (e.g. fibroblasts, chondroblasts):(e.g. fibroblasts, chondroblasts):




A substantial part of the volume in any tissue is constituted byextracellular space, which is largely filled by a network of macromolecules - the extracellular matrix.

Variations and the relative amounts of the different types of matrix macromolecules and the way they are organized give rise to a diversity of for ms and physical properties adaptedto the f unctional requirements of the particular tissue

(e.g. in the connective tissues the matrix can become calcifiedto for m har d str ucture of bone, or it can be transparent in cornea).

The cytoskeleton and extracellular matrix communicate

across the plasma membrane.

The cytoskeletons can or der the matrix macromolecules the cells secrete, and the matrix macromolecules can organize the cytoskeletons of cells that contact them.




a)a) PolysaccharidePolysaccharide glycosaminoglycans (GAGsglycosaminoglycans (GAGs):):--,,

usually covalently linked to proteins in the for m of usually covalently linked to proteins in the for m of

proteoglycans. Because they for m porous hydrated gels theyproteoglycans. Because they for m porous hydrated gels theyfill most of the extracellular space, providing mechanical fill most of the extracellular space, providing mechanical support to tissues and allowing the rapid diff usion of water support to tissues and allowing the rapid diff usion of water soluble molecules and the migration of cells.soluble molecules and the migration of cells.

1) 1) hyaluronic acidhyaluronic acid -- increased local production attracts water increased local production attracts water and thereby swells the matrix to facilitate cell migration and thereby swells the matrix to facilitate cell migration (inflammation, tissue repair, mor phogenesis), joint fluid, (inflammation, tissue repair, mor phogenesis), joint fluid, vitreous bodyvitreous body

2) 2) chondroitin sulphatechondroitin sulphate -- cartilage, cornea, bone skin, arteriescartilage, cornea, bone skin, arteries

3) 3) heparan sulphateheparan sulphate, , heparinheparin -- lung, arteries, cell surfaces, lung, arteries, cell surfaces, basal laminae, liver, mast cellsbasal laminae, liver, mast cells

4) 4) keratan sulphatekeratan sulphate -- cartilage, cornea, intervertebral disccartilage, cornea, intervertebral disc 1515



b ) Fi brous proteins:b ) Fi brous proteins:

11) str uctural proteins are decisive for the physical properties ) str uctural proteins are decisive for the physical properties of the tissue of the tissue -- collagen (strength), elastin (resilience)collagen (strength), elastin (resilience)

22) adhesive proteins increase attachment to ad jacent ) adhesive proteins increase attachment to ad jacent str uctures str uctures -- fibronectin (to the extracellular matrix), laminin fibronectin (to the extracellular matrix), laminin (attachment of epithelial cells to the basal lamina(attachment of epithelial cells to the basal lamina

The glycosaminoglycan and proteoglycan molecules for m a The glycosaminoglycan and proteoglycan molecules for m a

highly hydrated, gel like "ground substance" in which the highly hydrated, gel like "ground substance" in which the fibrous proteins are embedded. The aqueous phase per mits fibrous proteins are embedded. The aqueous phase per mits the diff usion of nutrients, metabolites and signaling the diff usion of nutrients, metabolites and signaling molecules between the blood and the tissue cells.molecules between the blood and the tissue cells.




Elementary construction unit of all live organisms.Elementary construction unit of all live organisms.

Procaryotic cellsProcaryotic cells Eucaryotic cellsEucaryotic cells -- D NA is kept in aD NA is kept in a

compartment separate from the cytoplasmcompartment separate from the cytoplasm

cytoplasm contains distinctive organellescytoplasm contains distinctive organelles ((richricharray of internal membranes, chloroplasts andarray of internal membranes, chloroplasts and

mitochondriamitochondria -- both are thought to have a both are thought to have a

symbiotic origin)symbiotic origin)

have a cytoskeletonhave a cytoskeleton ((actin filaments andactin filaments and

microtubules)microtubules)





Cells with a short half time -quick replacement ²

blood cells, epithels

cells with long half time(or without further multiplication) -a

dipose cells, glia

l cells, neurons, musclecells




Each adult human consist of about(± 60 -100,000,000,000,000) cells. These cells live in a

gigantic "commune".The human body contains about 200 different types of

cells. Each cell has a very specialized role.

Each cell type has a characteristic lifetime ,after which it commits suicide (apoptosis).

Some examples :

1. Neutrophils live about 1 day.

2. Intestinal epithelial cells live about 3 days .

3. Red blood cells live about 90 days

4. Neurons live as long as 90 years




Each cell is totally responsible for it's own" housekeeping" duties :

1. maintenance and repair

2. acquiring food from blood or lymph3. disposal of wastes into blood or lymph

4. synthesis and regulation of all its large biomolecules

5. dividing (when allowed to do so) by the process of mitosis ,and not dividing unless properly signaled (cellsthat divide without responding to normal signals produceCANCER ).

6. carrying out its own specialized tasks ,such as:contracting, making antibodies, firing nerve impulses,

secreting digestive enzymes, etc.Examples:

1 (nerve cells ) communications specialists);

2 (heart muscle cells ) contraction specialists)



7. Certain specialized cells must undergo a meiotic )sexual (cell division ,produce eggs or sperm, and atleast one such cell must find a partner if cellular life isto survive this particular individual.Example :human OVA and sperm cell

8. Each cell must differentiate from one commonancestral cell, the fertilized egg, by a complex processof differentiation and development. Example :Developing embryo ,starting from single fertilized egg .

9. Each cell must be able to communicate with othercells and respond appropriately to signals thatregulate its activity .




Tissue renewalTissue renewalMost of the tissues have to replace populations of lost cells, or Most of the tissues have to replace populations of lost cells, or

they have to rebuild their str ucture as a result of they have to rebuild their str ucture as a result of environmental factors.environmental factors.

1. Tissues with permanent cells1. Tissues with permanent cells

Cells generated in embr yo and retained through adult life Cells generated in embr yo and retained through adult life

(lens cells).(lens cells). Cells that partly remodel or rebuilt their str ucture (nerve Cells that partly remodel or rebuilt their str ucture (nerve

cells, heart muscle cells).cells, heart muscle cells).

Cells that undergo renewal of their component parts Cells that undergo renewal of their component parts (photoreceptors)(photoreceptors)

2. Tissues with cell renewal2. Tissues with cell renewal

Differentiated cells that divide by the simple duplication Differentiated cells that divide by the simple duplication ((hepatocyteshepatocytes))

Cells generated from stem cells (blood cells)Cells generated from stem cells (blood cells)DR.WAEL ELFARESIDR.WAEL ELFARESI 2222



Regulation of cell survivalRegulation of cell survivalIn many tissues, cells are genetically programmed toIn many tissues, cells are genetically programmed to

diedie if they do not receive specific signals for survival if they do not receive specific signals for survival

if the program is activated by some different specific if the program is activated by some different specific stimulistimuli

TheThe programmed cell deathprogrammed cell death (apoptosis) is activated(apoptosis) is activatedduringduring

development of tissuesdevelopment of tissues

turnover and renewal of cell populationsturnover and renewal of cell populations as a result of activity changes (hyperactivity or the loss as a result of activity changes (hyperactivity or the loss

of f unction)of f unction)

in in pathogeneticpathogenetic conditions (hypoxia, toxic stimuli, in conditions (hypoxia, toxic stimuli, in

tumors)tumors)DR.WAEL ELFARESIDR.WAEL ELFARESI 2323



Apoptosis (=delayed cell death)Apoptosis (=delayed cell death) is selective (some cell types are more sensitive is selective (some cell types are more sensitive -- vulnerable)vulnerable)

it is characterized by distinctive biochemical and mor phological it is characterized by distinctive biochemical and mor phological

featuresfeatures it requires macromolecular synthesis and activation of specific it requires macromolecular synthesis and activation of specific

genomic programsgenomic programs

at the end, cell are at the end, cell are phagocytosedphagocytosed by macrophages (or other by macrophages (or other neighboring cells) without secretion of the inflammationneighboring cells) without secretion of the inflammation--inducing inducing signalssignals

to activate the disposal mechanism, apoptotic cells change their to activate the disposal mechanism, apoptotic cells change their surface markerssurface markers

Cell necrosis (=rapid cell death) is the consequence of anCell necrosis (=rapid cell death) is the consequence of anacute injuryacute injury

swellingswelling lysislysis of cell organellesof cell organelles

splitting the cytosolic content into the extracellular spacesplitting the cytosolic content into the extracellular space

activation of an inflammator y responseactivation of an inflammator y response


extra cellular matrix

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