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Extracellular matrix

A network of protein

a collection ofextracellularmolecules
secreted by cells that provides structural and
biochemical support to the surrounding cells
cell adhesion, cell-to-cell communication and
differentiation are common functions of the
ECM
Most cells can secrete elements of the ECM
but many ECMs are built by fibroblasts
Examples of ECM:
-connective tissue, basal lamina,
cartilage, bone, plant/fungi cell walls,
myelin sheath,
Components of the extracellular matrix

Proteins/glycoproteins

bind to different combinations of


macromolecules on cell membranes (e.g.
integrins, cadherins) and other ECM elements

Examples include:

-collagen, elastin, fibronectin, laminin


Proteins can provide elastic properties in many
tissues (e.g. elastin)
glycosoaminoglycans (GAGs) proteoglycan are
major proteins
GAGs differ in physical properties (e.g. size,
flexibility, hydration).

Composed of repeating sugar + amino sugar units


(e.g. N-acetylglucosamine, N-acetylgalactosamine)

They occur in long strings, often attached to


proteins

Examples include:
-hyaluronan, chondroitin sulfate, heparan sulfate,
keratan sulfate
GAGs attract a great deal of water

Hydroxyl groups form hydrogen bonds

many negative charges attract clouds of cations (Na+) that

induce an osmotic movement of water

These hydrated gels resist compression (useful for joints).


Components of the extracellular matrix
Proteoglycans (made of both proteins and
GAGs) also differ in physical properties

Synthesized in Golgi prior to secretion

In addition to structural roles,


proteoglycans can also bind hormones
(e.g., inflammatory chemokines, FGF,
TGFb) to alter cell signaling pathways

Examples include:
ECM proteins, GAGs, and proteoglycans

Green-protein
Red-GAG
COMPONENT PROPERTIES
Hyaluronan(glucuronic acid Attracts water and fills
and N-acetylglucosamine) spaces between cells with
non-compressible gel
(found around joints)

Aggrecan Each aggrecan can be


attached to a hyaluronan
backbone to form an
aggrecan aggregate

Collagen Collagen proteins (trimers)


are then cross-linked to
form collagen fibers
(stiff, not very elastic)

Fibronectin able to bind different


proteins/GAGs (e.g.
integrins, collagen, etc)
Cells control the synthesis of ECM by
altering gene expression and co-
translational import and secretion

They also control the degradation of


the ECM by secreting and
activating/inactivating extracellular
enzymes.
Matrix Metallo Protinases(MMPs)
Cells that need to migrate must first
break down the connections to the ECM
(e.g. tissue repair, metastasis of tumors)
MMPs capable of degrading ECM proteins
MMPs can be:
-secreted in active form (collagenase)
- secreted as inactive form (e.g.
plasminogen is inactive until it is
modified by plasminogen activators)
-activated when cells stop secreting
TIMPs (tissue inhibitors of

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