LINK

Tissues do not consist only of cells, a large part of their volume is extracellular space,
filled by a mesh of macromolecules that constitute THE EXTRACELLULAR MATRIX (ECM)

- strength and adequate rigidity to tissues; - transmission of information between the

intra- and extracellular space; - control of the passage of molecules or ions through cell layers; -
allow the movement of ions and molecules between the cytoplasm of neighboring cells- gap
junctions)
 Variation in the relative density of cells and ECM in different tissues

Relative volumes occupied by cells and surrounding matrix vary greatly among different animal tissues.
(a) Dense connective tissue – contains mostly extracellular matrix containing tightly packed ECM fibers (pink) interspersed with
rows of relatively sparse fibroblasts (cells that synthesized ECM)
(b) Sparse connective tissue – squamous epithelial cells tightly packed into a quilt-like pattern with little ECM between the cells
 Integrating Cells into Tissues
Cell-Cell and Cell–Extracellular Matrix Adhesion
• Cell-cell and cell–extracellular matrix (ECM) interactions are critical for
assembling cells into tissues, controlling cell shape and function, and
determining the developmental fate of cells and tissues.
• Cell-adhesion molecules (CAMs) mediate direct cell-cell adhesions
(homotypic and heterotypic), and adhesion receptors mediate cell-
matrix adhesions.
• ECM is a dynamic, complex meshwork of proteins and polysaccharides
that contributes to the structure and function of a tissue.
 MEDIATORS AND
MECHANISMS OF CELL
ADHESION, CELL INTERACTION
AND COMMUNICATION
 Cell Adhesion Molecules-CAMs

CELL/CELL OR CELL/EXTRACELLULAR MATRIX

TYPES OF BINDING BETWEEN ADHESION MOLECULES - CELL-CELL
MAJOR FAMILIES OF CELL-ADHESION MOLECULES (CAMS)/ADHESION
RECEPTORS
CADHERINS (LINK: more information)
➢ Are calcium-dependent.
➢ Mediate cell-cell adhesions in adherens junctions and
desmosomes
➢ Play a fundamental role in tissue formation and maintenance of
tissue integrity.
➢ They are the main adhesion molecules present in embryonic
tissues (E-cadherins are the first to be expressed during
development).
➢ In the plasma membrane they associate and form dimers or
oligomers.
➢ Cadherins bind to other cadherins of the same type - homophilic
binding. Weak but repeated binding leads to strong adhesion.
➢ All cells express cadherins.
 CADHERINS

Cadherin contains a repeat sequence (5x). There are Ca2+ binding sites between each repeat. Ca2+
binding induces rigidity, allowing binding to another dimer. If Ca2+ is removed, the extracellular
part of the protein becomes flexible and is degraded by proteolytic enzymes
E-cadherin mediates Ca2+-dependent adhesion on in vitro cell
culture
 E-CADHERIN MEDIATES ADHESIVE CONNECTIONS IN CULTURED
EPITHELIAL CELLS

Epithelial cells – expressing E-cadherin fused to green fluorescent protein (GFP). Cells were mixed in a
Ca2+-containing medium. Forms bicellular junctions and tricellular junctions
INTERACTIONS OF CLASSICAL CADHERINS IN TYPICAL ADHERENS JUNCTIONS
Trans (intercellular) and cis (on the same cell)
interactions of classical cadherins
Organization of the cadherin superfamily

Actin cytoskeleton

Intermediate
filaments

The main structural and functional

characteristics of the cadherin
subfamilies and types are indicated.
Representative examples are shown,
with gene denomination of some of
them in brackets. The main structural
domains and schematic structure of the
different cadherin types are shown at
the right.

doi: 10.1387/ijdb.041794hp
E-cadherin activity is lost during the epithelial-to-mesenchymal
transition and during cancer progression

Epithelial mesenchymal transition is also

associated with Pathology Immunohistochemical staining (dark brown)
for E-cadherin.
INTEGRINS
➢ Responsible for firm adhesion.

➢ Localised on the surface of leukocytes,

epithelial cells, other cells

➢ Bind to CAMs (cell adhesion molecules) on the

endothelium.

➢ Heterodimeric transmembrane glycoproteins

(chains  and β).

➢ Cell-cell or cell-extracellular matrix adhesion.

➢ Bind various proteins (laminin and fibronectin
of the ECM). This binding is dependent on
calcium and magnesium concentration.
➢ Bind to intracellular proteins (e.g. talin).
 Selected Vertebrate Integrins
Subunit Primary Cellular
Ligands
Composition Distribution
α1β1 Many types Mainly collagens
α2β1 Many types Mainly collagens; also laminins
α3β1 Many types Laminins
α4β1 Hematopoietic cells Fibronectin; VCAM-1
α5β1 Fibroblasts Fibronectin
α6β1 Many types Laminins
αLβ2 T lymphocytes ICAM-1,1CAM-2
Serum proteins (e.g., C3b, fibrinogen, factor X);
αMβ2 Monocytes
ICAM-1
Serum proteins (e.g., fibrinogen, von Willebrand
αIIbβ3 Platelets factor, vitronectin); fibronectin
α6β4 Epithelial cells Laminin
NOTE: The integrins are grouped into subfamilies having a common β subunit. Ligands shown in red are CAMs; all others are ECM
or serum proteins. Some subunits can have multiple spliced isoforms with different cytosolic domains. SOURCE: Data from R. O. Hynes, 1992,
Cell 69(1):11.
Integrin adhesion receptor–mediated signaling pathways control diverse
cell functions

ACTIVATION OF INTRACELLULAR
SIGNALLING PATHWAYS.

Binding of integrins to their ligands induces conformational

changes in their cytoplasmic domains, directly or indirectly
altering their interactions with cytoplasmic proteins (outside-in
signaling). These cytoplasmic proteins include adapter proteins
(e.g., talins, kindlins, paxillin, vinculin) and signaling kinases that
transmit signals via diverse signaling pathways, thereby
influencing CELL PROLIFERATION, CELL SURVIVAL,
CYTOSKELETAL ORGANIZATION, CELL MIGRATION, AND
GENE TRANSCRIPTION.

Components of several signaling pathways, some of which are

associated directly with the plasma membrane, are shown in
green boxes. Many of the components of the pathways shown
here are shared with other cell-surface-activated signaling
pathways (e.g., receptor tyrosine kinases shown on the right).