 Most of the cells in multicellular organisms are organized into

cooperative assemblies - tissues, which are in turn associated in

various combinations as larger functional units called organs.

 The cells in tissues are in direct contact with neighboring cells

and very often they are linked to each other at specialized
intercellular junctions.

 Some part of the cell is usually in contact with a complex

network of secreted extracellular macromolecules, called the
extracellular matrix..

 This matrix helps to hold cells and tissues together, and it

provides an organized lattice within which cells can migrate and
interact with one another.
DR.WAEL ELFARESI 1
 Cell - Cell Adhesions
 Cell surface molecule protein: Integrin
 Binds and mechanically fixes cells to ECM
 Serves in signal transduction also
 At focal adhesion --> it is part of the Focal Adhesion Kinase Pathway
 triggers cell anchoring

 Cell adhesion molecules: CAM's; usually glycoproteins

 Cadherens: calcium dependent
 important in initial attachment such as in development of cells,
 maintaining the structure and integrity of cells
 Selectins
 Ig superfamily
 N - CAM's, nerve cells and calcium independent

DR.WAEL ELFARESI 2
Cells
Cells are
are joined
joined by
by aa variety
variety
of
of intracellular
intracellular junctions
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 through
intracellular spaces.

– Gap junctions (found in animals): formed by two connecting

protein rings embedded in cell membrane of adjacent 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
DR.WAEL ELFARESI 4
DR.WAEL ELFARESI 5
In biology, extracellular matrix (ECM)
is any material part of a tissue that is
not part of any cell.

Most of the cells in multicellular

organisms are surrounded by a
complex mixture of nonliving material
that makes up the extracellular matrix
(ECM).
DR.WAEL ELFARESI 6
Most normal vertebrate cells cannot survive
unless they are anchored to the
extracellular matrix. This anchorage
dependence is often lost when a cell turns
cancerous.
For example, (HeLa cells, are among the
few types of vertebrate cell that can be
grown in liquid culture.)

DR.WAEL ELFARESI 7
 functions of The ECM
Given this diversity, it can serve many number of
functions.
1. providing support and anchorage for the cells.
2. The ECM functions in a cell's dynamic behavior.
3. The integrins transmit mechanical stimuli from
the ECM to the cytoskeleton.
4. Many cells bind to components of the
extracellular matrix. This cell-to-ECM adhesion
is due to specific cell surface adhesion proteins
known as cellular adhesion molecules (CAM).
DR.WAEL ELFARESI 8
ECM contains many components:
 proteins such as fibrin and elastin,
 minerals such as hydroxylapatite (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 in the ECM is collagen.

DR.WAEL ELFARESI 9
 In plants,
the ECM is primarily composed of cellulose.
In arthropods and fungi,
the ECM is largely composed of chitin.

Extracellular matrix is the defining feature of

connective tissue.

DR.WAEL ELFARESI 10
 Connecting Cells to the ECM
 Cells attach to the ECM by means of
transmembrane glycoproteins called integrins.

 The extracellular portion of integrins binds to

various types of ECM proteins:
• collagens
• laminins
• fibronectin

 The intracellular portion binds to the

actin filaments of the cytoskeleton.
DR.WAEL ELFARESI 11
 In some cases cells are attached to the matrix
at specialized regions of their plasma
membrane called cell-matrix junctions.

Two extreme examples:

 Connective tissues - extracellular matrix is plentiful and cells
are sparsely distributed within it. The matrix, rather than the
cells, bears most of the stresses to which the tissue is
subjected.( bone)

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

extracellular matrix is scanty. The cells themselves bear most
of the stresses by means of strong intracellular protein
filaments that criss-cross through the cytoplasm of each cell
and bind to specialized cell junctions.
DR.WAEL ELFARESI 12
 The macromolecules that
constitute the extracellular
matrix are mainly secreted
locally by cells in the matrix
(e.g. fibroblasts, chondroblasts):

DR.WAEL ELFARESI 13
A substantial part of the volume in any tissue is constituted by
extracellular 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 forms and physical properties adapted
to the functional requirements of the particular tissue
(e.g. in the connective tissues the matrix can become calcified
to form hard structure of bone, or it can be transparent in
cornea).

 The cytoskeleton and extracellular matrix communicate

across the plasma membrane.

 The cytoskeletons can order the matrix macromolecules the

cells secrete, and the matrix macromolecules can organize
the cytoskeletons of cells that contact them.
DR.WAEL ELFARESI 14
a) Polysaccharide glycosaminoglycans (GAGs):-,
usually covalently linked to proteins in the form of
proteoglycans. Because they form porous hydrated gels they
fill most of the extracellular space, providing mechanical
support to tissues and allowing the rapid diffusion of water
soluble molecules and the migration of cells.

1) hyaluronic acid - increased local production attracts water

and thereby swells the matrix to facilitate cell migration
(inflammation, tissue repair, morphogenesis), joint fluid,
vitreous body

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

3) heparan sulphate, heparin - lung, arteries, cell surfaces,

basal laminae, liver, mast cells

4) keratan sulphate - cartilage, cornea, intervertebral disc 15

b) Fibrous proteins:

1) structural proteins are decisive for the physical properties

of the tissue - collagen (strength), elastin (resilience)

2) adhesive proteins increase attachment to adjacent

structures - fibronectin (to the extracellular matrix), laminin
(attachment of epithelial cells to the basal lamina

 The glycosaminoglycan and proteoglycan molecules form a

highly hydrated, gel like "ground substance" in which the
fibrous proteins are embedded. The aqueous phase permits
the diffusion of nutrients, metabolites and signaling
molecules between the blood and the tissue cells.
DR.WAEL ELFARESI 16
Elementary construction unit of all live organisms.
 Procaryotic cells
 Eucaryotic cells - DNA is kept in a compartment
separate from the cytoplasm
cytoplasm contains distinctive organelles (rich array of
internal membranes, chloroplasts and mitochondria -
both are thought to have a symbiotic origin)
have a cytoskeleton (actin filaments and microtubules)

DR.WAEL ELFARESI 17
 Cells with a short half time - quick
replacement –
blood cells, epithels

cells with long half time

(or without further multiplication) - adipose cells,
glial cells, neurons, muscle cells

DR.WAEL ELFARESI 18
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:
l Neutrophils live about 1 day.
l Intestinal epithelial cells live about 3 days.
l Red blood cells live about 90 days
l Neurons live as long as 90 years
DR.WAEL ELFARESI 19
Each cell is totally responsible for it's own "housekeeping" duties:
1. maintenance and repair
2. acquiring food from blood or lymph
3. 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 (cells
that divide without responding to normal signals produce
CANCER(.
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)
DR.WAEL ELFARESI 20
7. Certain specialized cells must undergo a meiotic
(sexual) cell division, produce eggs or sperm, and at
least one such cell must find a partner if cellular life is
to survive this particular individual.
Example: human OVA and sperm cell

8. Each cell must differentiate from one common

ancestral cell, the fertilized egg, by a complex process
of differentiation and development. Example:
Developing embryo, starting from single fertilized egg.

9. Each cell must be able to communicate with other

cells and respond appropriately to signals that
regulate its activity.
DR.WAEL ELFARESI 21
 Tissue renewal
Most of the tissues have to replace populations of lost cells, or
they have to rebuild their structure as a result of
environmental factors.

1. Tissues with permanent cells

 Cells generated in embryo and retained through adult life
(lens cells).
 Cells that partly remodel or rebuilt their structure (nerve
cells, heart muscle cells).
 Cells that undergo renewal of their component parts
(photoreceptors)

2. Tissues with cell renewal

 Differentiated cells that divide by the simple duplication
(hepatocytes)
 Cells generated from DR.WAEL
stem cells (blood cells)
ELFARESI 22
 Regulation of cell survival
In many tissues, cells are genetically programmed to die
 if they do not receive specific signals for survival
 if the program is activated by some different specific stimuli

The programmed cell death (apoptosis) is activated

during
 development of tissues
 turnover and renewal of cell populations
 as a result of activity changes (hyperactivity or the loss of
function)
 in pathogenetic conditions (hypoxia, toxic stimuli, in tumors)

DR.WAEL ELFARESI 23
Apoptosis (=delayed cell death)
 is selective (some cell types are more sensitive - vulnerable)
 it is characterized by distinctive biochemical and morphological
features
 it requires macromolecular synthesis and activation of specific
genomic programs
 at the end, cell are phagocytosed by macrophages (or other
neighboring cells) without secretion of the inflammation-inducing
signals
 to activate the disposal mechanism, apoptotic cells change their
surface markers

Cell necrosis (=rapid cell death) is the consequence of an

acute injury
 swelling
 lysis of cell organelles
 splitting the cytosolic content into the extracellular space
 activation of an inflammatory response
DR.WAEL ELFARESI 24