The document summarizes the key components and functions of the extracellular matrix (ECM). It describes the ECM as a network of proteins and macromolecules that provides structural and biochemical support to surrounding cells. It identifies two basic forms of ECM - the interstitial matrix present in connective tissue and the basement membrane that lies beneath epithelium. It also outlines the major components of ECM including collagens, elastin, proteoglycans, hyaluronan, fibronectin and laminin. Finally, it discusses the roles of ECM in mechanical support, cell proliferation, tissue regeneration and cellular interactions.

1. Extracellular Matrix
and Its Components
ECM

2. Extracellular matrix (ECM)
 Extracellular matrix (ECM) is a network of extracellular
macromolecules, such as collagen, enzymes, and
glycoproteins, that provide structural and biochemical support
to surrounding cells
 ECM includes the interstitial matrix and the basement
membrane
 Gels of polysaccharides and fibrous proteins fill the interstitial
space
 This gel act as a compression buffer against the stress placed
on the ECM

3. General Structure of Extracellular
Matrix
 Animal cells embedded in an extracellular matrix Basal
laminae: thin layer on which epithelial cells rest.
 Also surrounds muscle cells, adipose cells, and
peripheral nerves most abundant in connective tissues
 Connective tissue loose connective tissue Bone
tendon cartilage

4. Extracellular matrix (ECM)
 Extracellular matrix (ECM) is a network
of interstitial proteins that constitutes a
significant proportion of any tissue.
ilIustration depicting extracellular matrix in relation to
epithelium, endothelium and connective tissue

6. FUNCTIONS OF ECM
 Mechanical support- For cell anchorage and cell migration, and
maintenance of cell polarity.
 Control of cell proliferation- By acting as a depot of latent growth
factors, binding and displaying growth factors, and signaling
through cellular receptors.
 Scaffolding for tissue renewal- Integrity of ECM is critical for the
organized regeneration of tissues.
 So ECM disruption results in defective tissue regeneration and
repair (eg. Cirrhosis of Liver).

7. FUNCTIONS OF ECM
Establishment of tissue microenvironments-
Basement membrane acts as boundary
between epithelium and connective tissue, and
is also functional.
 Cellular interaction- For maintaining normal
tissue architecture.

8.  ECM is important for cell adhesion and serve as a
reservoir for growth factors, thus, ECM regulates the
proliferation, movement, and differentiation of the
cells living within it.
 Synthesis and degradation of ECM accompanies
morphogenesis, wound healing, chronic fibrotic
processes, and tumor invasion and metastasis

9. TWO BASIC FORMS OF ECM
 ECM occurs in two basic forms:
interstitial matrix and basement membrane
 1- Interstitial Matrix:
 present in the spaces between cells in connective tissue;
 it is synthesized by mesenchymal cells (e.g., fibroblasts) and tends to
form a three-dimensional, amorphous gel.
 Its major constituents are fibrillar and nonfibrillar collagens, as well
as fibronectin, elastin, proteoglycans, hyaluronate, and other
elements

10. The basement membrane:
lies beneath the epithelium
It is synthesized by overlying epithelium and
underlying mesenchymal cells
Its major constituents are amorphous
nonfibrillar type IV collagen and laminin

11. COMPONENTS OF ECM
 Components of ECM are categorized into 3 groups of proteins;
 1) Fibrous structural proteins- Collagens, Elastins & Fibrillin.
Confer tensile strength and recoil.
 2) Water-hydrated gels- Proteagylcans & Hyaluronan
Permit compressive resistance and lubrication.
 3) Adhesive gl roteins & r y- F bronectin, Laminin & integan
Connect ECM elements to one another and to cells.
 4) Water - 65%

12. Collagens
 Collagens are fibrous structural proteins that confer tensile strength.
 Collagens are composed of three separate polypeptide chains braided into a ropelike
triple helix.
 About 30 collagen types have been identified
 Some collagen types (e.g., types I, II, III, and V) form fibrils by virtue of lateral cross-
linking of the triple helices. These are called the fibrillarcollagens, and form a major
proportion of the connective tissue in healing wounds and particularly in scars
 Other collagens are nonfibrillar and present in basement membrane (type IV)
 The tensile strength of the fibrillar collagens derives from their cross-linking, which is the
result of covalent bonds.
 This process is dependent on vitamin C; therefore, children with vitamin C
deficiencyhave skeletal deformities, bleed easily because of weak vascular wall basement
membrane, and heal poorly

13. Elastin
 the ability of tissues to recoil and return to a baseline
structure after physical stress is conferred by elastic
tissue.
 This is especially important in the walls of: vessels , the
uterus, skin, and ligaments.

14. Proteoglycans and Hyaluronan
 Proteoglycans form highly hydrated compressible gels conferring resilience
and lubrication (such as in the cartilage in joints).
 They consist of long polysaccharides called glycosaminoglycans (examples
are dermatan sulfate and heparan sulfate) linked to a protein backbone.
 Hyaluronan a huge molecule composed of many disaccharide repeats
without a protein core, is also an important constituent of the ECM.
 Because of its ability to bind water, it forms a viscous, gelatin-like matrix

15. Adhesive glycoproteins and adhesion
receptors
 Adhesive glycoproteins and adhesion receptors are structurally diverse
molecules involved in cell-to-cell adhesion, the linkage between cells and
ECM, and binding between ECM components.
 The adhesive glycoproteins include fibronectin (major component of the
interstitial ECM) and laminin (major constituent of basement membrane).
 The adhesion receptors, also known as cell adhesion molecules (CAMs), are
grouped into four families: immunoglobulins, cadherins, selectins, and
integrins

16. Fibronectin
 Fibronectin is a large disulfide-linked heterodimer
 synthesized by a variety of cells, including fibroblasts, monocytes, and
endothelium.
 Main adhesion protein of connective tissue
 Fibronectins can bind to a wide spectrum of ECM components (e.g.,
collagen, fibrin, heparin, and proteoglycans) and can also attach to cell
integrins.
 Fibronectin mRNA has two splice forms, which generate:
 1- tissue fibronectin forms fibrillar aggregates at wound healing sites 2-
plasma fibronectin binds to fibrin to form the provisional blood clot of a
wound, which serves as a base for ECM deposition and re-epithelialization

17. Laminin
 Laminin is the most abundant glycoprotein in
basement membrane.
 Adhesion protein of basal laminae
 connects cells to underlying ECM components
such as type IV collagen and heparan sulfate,
mediating attachment to basement membrane.
 laminin can also modulate cell proliferation,
differentiation, and motility.

18. Cell-Matrix Interactions
 Integrins: major cell surface receptors, involved in
attachment of cells to the extracellular matrix
 Transmembrane proteins, heterodimer of α and β
subunits (18α, 8β)
 Bind to short aa in,
Collagen
Fibronectin
laminin
 also anchor the cytoskeleton to the extracellular
matrix

19. Cell-Matrix Junctions
 Two types of cell-matrix junction
 Focal adhesions:
 bundles of actin filaments are anchored to β
subunits of integrins via α-actinin
 Vinculin via talin
 Assembly of focal adhesions
 Focal complex: small group of integrins
 RecruiteTalin, Vinculin, α-actinin and Formin
 Formin initiates actin bundles

20. Focal adhesions are reversible
 Integrins can reversibly bind matrix components
 change conformation between active and inactive states
 Inactive state: integrin heads turned close to cell surface
 Cell signaling extends heads to matrix
 Migrating cells: focal adhesions form at the leading edge

21. Cell-Matrix Junctions: Hemidesmosomes
 Hemidesmosomes anchor epithelial cells
to the basal lamina
 α6 β4 integrins bind to lamins
 long cytoplasmic tail of β subunit binds
to intermediate filaments via Plectin and
BP230 and BP180 (similar to
transmembrane collagens)