Interactions Between Cells and Their Environment

Interactions Between Cells
and Their Environment

Introduction
Cells don’t exist alone.
Cells interact with extracellular material
to form defined tissues.
These interactions are crucial to the
formation of epithelial tissue and
connective tissue, which are crucial for
various cellular activities.

Introduction (Cont.)
Cell migration, cell growth, cell
differentiation, 3-D organization of
tissues and organs that emerges during
embryonic development.

Overview of cell organization into
tissues
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7.1 The Extracellular Space (1)
The glycocalyx (cell
coat) is formed from
carbohydrate
projections form the
plasma membrane.
Outer surface of the
plasma membrane

7.1 The Extracellular Space (cont.)
Gycocalyx
Mediate cell-cell and cell-substratum
interactions
Provide mechanical protection to cells
Barrier to particles moving toward
plasma membrane
Bind important regulatory factors

The Extracellular Space (cont.)
The extracellular matrix (ECM) is an
organized network of proteins and
polysaccharides beyond the plasma
membrane.
“Glue” that holds cells together
It often plays a regulatory role in
determining shape and activities of
the cell.

 ECM (continued)
The basement membrane (basal lamina) is
a continuous sheet that underlies epithelial
tissue and surrounds blood vessels.
Helps maintain cells attached.
Serves as substratum for cell migration.
Forms a barrier to macromolecules.

Extracellular matrix
Gel-like “ground substance”
Primarily made of polysaccharides
Gylycosaminoglycans (GAGs)
proteoglycans
Fibrous proteins
Collagen, laminin, elastin, fibronectin
Structure and adhesive functions

 Collagens – fibrous glycoproteins found only
in the ECM.
Collagen is the most abundant protein in
the human body.
Provide high tensile strength.
Each collagen is restricted to particular
locations in the body.
All collagens are a trimer of polypeptide
chains (α chains) and 3 polypeptide chains
are wound around each other.

Major types of collagen
 Type I collagen
 The chief component of tendons,
ligaments, and bones.
 Type II collagen
Represents more than 50% of the protein in
cartilage and is the major component of the
vitreous body of the eye.
 It is also used to build the notochord of
vertebrate embryos.

 Type III collagen
 Strengthens the walls of hollow structures like
arteries, the intestine, and the uterus.
 Type IV collagen
 Forms the basal lamina of epithelia. (The basal
lamina is often called the basement membrane.)A
meshwork of Type IV collagens provides the filter
for the blood capillaries and the glomeruli of the
kidneys.

 Collagens (continued)
Provide the insoluble
framework that
determines
mechanical
properties of the
matrix.
Abnormalities in
collagen formation
lead to serious
disorders.

Collagens type I, II, III are fibrillar
collagens
Assemble into rigid, cable-like fibrils
(assembles like fibers)
Example: tendon – collagens are
parallel to tendons thus parallel to
pulling actions

Abnormalities in
fibrillar collagens
formation can lead to
serious disorders
Mutation in in genes
encoding type I
collagen can produce
osteogenesis imperfecta
Extremely fragile bones,

 Mutation in genes encoding
type II alter the properties of
cartilage tissue causing
dwarfism and skeletal
deformities
 Mutations in other collagens
genes that are related in
collagen matrix structure
can lead to Ehler-Danlos
sydromes

Not all collagens form
fibrils.
Collagen type IV is
non-fibrillar, and is
restricted to the
basement membrane.

 Mutations in type IV
collagen genes causes
Alport syndrome
A kidney disease in
which glomerular
basement
membrane is
disrupted

Proteoglycans – protein-polysaccharide
complex, with a core protein attached to
glycosaminoglycans (GAGs).
GAGs
Have a repeating disaccharide
structure.
Negatively charged

Negatively charged GAGs attract lots of
cations, which in turn attract water
forming a porous, hydrated gel.
Function:
to be able to withstand compressional
forces through hydration and swelling
pressure (turgor) to the tissue

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Structure of a proteoglycan complex

Forms complement to collagen molecule
Together, they give cartilage and other
extracellular matrices strength and
resistance to deformation
Example: ECM of bones
Collagen + Proteoglycans + calcium
sulfate ions = bones
GAG chains of proteoglycans also act as

 Fibronectin (Fn)
 Multiple binding domains
Complex proteins that binds to multiple
substrates
 Helps cells attach to matrix
 Fn has binding sites for other components of
the ECM.
 RGD

 Fibronectin (FN) is involved in many cellular
processes, including tissue repair,
embryogenesis, blood clotting, and cell
migration/adhesion.
 Fibronectin sometimes serves as a general cell
adhesion molecule
 FN also can serve to organize cellular

 Laminins – extracellular
glycoproteins consisting
of three polypeptide
chains linked by disulfide
bonds.
Help cell migration
during development.
Components of
basement membranes.

 Dynamic Properties
The ECM can be stretched during tension.
ECM materials degraded by matrix
metalloproteinases (MMPs).
MMPs possibly involved in tissue remodeling,
embryonic cell migration, wound healing , and
formation of blood vessels.
Excessive MMPs causes arthritis, hepatitis,
atherosclerosis, tooth and gum disease and
tumor progression

7.2 Interactions of Cells with
Extracellular Materials
 Integrins – family of membrane proteins
composed of heterodimers with α and ß
subunits.
Have a major role in integrating
extracellular and intracellular
environments.
Another role is adhesion of cells to their
substratum or other cells.

Interactions of Cells with Extracellular
Materials (cont.)
 Integrins (continued)
Linkage between
integrins and their
ligands mediates
adhesion between
cells and their
environment.
Binding of proteins to
integrins is facilitated
by tripeptide RGD.

Materials (cont.)
Integrins (continued)
Cytoplasmic domains of integrins
contain binding sites for a variety of
cytoplasmic proteins.
Integrins make the connection
between the ECM and the
cytoskeleton.

Blood clotting
 Injury conformational
change in platelets’
integrin activation
inc. fibrinogen
affinity aggregation of
platelets

Synthetic RGD peptides
-> inhibit blood clot

Materials (cont.)
Focal adhesions are found at the cell
membrane where the cytoskeleton
interacts with proteins of the
extracellular matrix
Focal adhesions – scattered, discrete
sites for cell adhesion to their
substratum in vitro.
They may act as a type of sensory
structure.

 The clustering of integrins at these sites
attracts a large complex of proteins and
initiates intracellular regulatory processes, by
which such events as cell migration and
anchorage-dependent differentiation are
controlled.
 Focal adhesion kinase (FAK) is a protein
tyrosine kinase which is recruited at an early
stage to focal adhesions and which mediates
many of the downstream responses.

Interactions of Cells with
Extracellular Materials (cont.)
Hemidesmosomes are cell-substratum
adhesion sites that connect the
extracellular matrix to the keratin
cytoskeleton
 basal attachments of epithelial cells to
the basement membrane in vivo.
Contain a dense plaque with filaments
consisting of keratin.

form rivet-like links between cytoskeleton and
extracellular matrix components such as the basal
lamina that underlie epithelia

7.3 Interaction of Cells with Other
Cells
 Cells have surface-
recognition sites that
maintain
organization

Interaction of Cells with Other Cells
(cont.)
Selectins – family
of integral
membrane
glycoproteins that
bind to sugars on
the surface of
cells.

(cont.)
 Selectins (continued)
Contain a small cytoplasmic domain, a
single membrane-spanning domain, and a
large extracellular segment.
Three types:
E-selectin – on endothelial cells.
P-selectin – on platelets and endothelial
cells.

(cont.)
 Immunoglobulin
superfamily (IgSF) –
most proteins are
involved in immune
functions.
Most IgSF molecules
mediate interaction
of lymphocytes with
cells required or
immune response.

TIGHT JUNCTIONS

located at the apical end of the
junctional complex between adjacent
epithelial cells

sites where integral proteins of two
adjacent membranes meet

block the diffusion of solutes and
water

“fences”

Interactions Between Cells and Their Environment


claudin – major structural component

claudin – 16
− expressed in TAL

claudin – 1
− prevents water loss

blood-brain barrier
− prevents drugs from entering CNS

GAP JUNCTIONS

sites for intercellular communication

plasma membranes come very close,
but no contact

composed of connexin subunit:
connexon

allow molecules less than 1000
daltons

relatively nonselective


channel closure is triggered by
phosphorylation of connexin

have a potential to integrate individual
cells into functional unit

allow cells to share metabolites


connexons
− differ in conductance, permeability,
and regulation
− promote or prevent communication
− mutation resulting to disorder might
cause defects

tunneling nanotubules
− conducting cell surface proteins

PLASMODESMATA

cytoplasmic channels that pass
through cell walls

desmotubule

sites of cell to cell communication

capable of dilation

CELL WALLS


bacteria, fungi, plants

gives polyhedral shape

“skeleton”

source of signal

cellulose
− fibrous component of cell wall

protiens and pectin
− provide matrix


cellulose
− cellulose synthase
− organized into rod-like microfibrils

provide rigidity

resistance to tensile forces
− polymerized at cell surface

matrix
− synthesized in the cytoplasm
− three types of macromolecules


hemicelluloses
− bind to the surfaces of cellulose
microfibrils

pectins
− holds water

proteins
− expansins – cell growth
− elongation

CELL WALLS

thin cell plate

provide suporrt

primary walls

secondary walls

lignin
− structural support
− in xylem, move water through the
plant

Interactions Between Cells and Their Environment

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