PLASMA MEMBRANE

(CELL MEMBRANE)
 I. DEFINIT1ON

• The plasma membrane is a dynamic structure that separates the

intracellular medium (hyaloplasm or cytosol) from the extracellular
medium.

• The membrane is a complex set of lipids, proteins and sugars that

regulate the exchange between the cell and its environment.

• The key components of the biological membrane are phospholipids.

 II. STRUCTURE AND ULTRASTRUCTURE

• 1. Photonic microscopy: the plasma membrane appears as a thin line

or as a dense area that separates the intracellular medium from the
extracellular medium.
2. Transmission Electron Microscopy (TEM)
• The observation of thin sections at high magnification shows that the
membrane is 75 A◦ thick,
• formed of three sheets or layers:
two dark lipophobic (hydrophilic) layers separated by a light lipophilic
layer (hydrophobic).
The dense outer layer is covered by a thin glycoprotein film, the
fibrils of which are perpendicular to the membrane: this is the "cell
coat" or glycocalyx.
This is responsible for the asymmetry of the membrane.
 3. Scanning Electron Microscope (SEM)
• Observation of replicas: after cryostripping, observation of the
replica shows the plasma membrane cleaved into two hemi-
membranes: an outer exoplasmic hemi-membrane and an inner hemi-
membrane on the hyaloplasmic side.
 III. CHEMICAL COMPOSITION

According to the fluid mosaic model, the cell membrane is made up

mainly of lipids, proteins and small proportions of carbohydrates.
the lipids (mainly phosphoglycerolipids) are organised in a bilayer
the membrane thus presents a two-dimensional fluid structure, made
up of a "mosaic" of various proteins incorporated into or attached to
this bilayer.
Membrane carbohydrates always exist in the form of residues
associated with proteins (glycoproteins) or lipids (glycolipids) and
oriented towards the outside of the cell.
• These proportions vary from cell to cell, but in general the
protein/lipid mass ratio is close to 1 for all plasma membranes ;
whereas most endo-membranes are richer in protein.
1-Membrane lipids

• Lipids give the membrane its skeleton and characteristic structure.

• They have the property of associating via hydrophobic bonds to form
a lipid double layer by self-assembly.
• On average, lipids have a much lower molar mass than proteins.
• Depending on the type of membrane, there are between 10 and 100
lipid molecules for one protein molecule. Lipids therefore make up the
vast majority of membrane molecules.
1-1. Different classes of membrane lipids

• There are three main categories of membrane lipids: phospholipids,

glycolipids and sterols (cholesterol).

a) Phospholipids:
Phospholipids all have a
hydrophilic head (phosphate and
specialised group) and a
hydrophobic tail (glycerol and
fatty acids). The most classic
example of a phospholipid is
phosphatidylcholine.
b) Cholesterol :
• It is only present in the membranes of animal cells; in fact, it is absent
from plant cells (it is replaced by other types of sterols: sitosterol and
stigmasterol) and bacteria.
• It represents ¼ of membrane lipids. It is made up of a polar group and
a steroid group. Changes in its proportions affect membrane fluidity.
C: Glycolipids

Glycolipids 5% membrane components, essentially resulting

from the esterification or amidification of fatty acids by oses or
sugars. Two types: glyceroglycolipid and sphingolipid
 1-2.Membrane lipid properties
Fluidity: the fluidity of the membrane depends on the unsaturation of the
phospholipids, the amount of cholesterol and the temperature. Unsaturation of
hydrocarbon chains increases membrane fluidity.

Self-assembly: phospholipids can be organised or assembled into bilayers thanks to their

amphiphilic or bipolar nature (hydrophilic head and hydrophobic tail).

Mechanical stability: Cholesterol reinforces the solidity of the membrane.

It is placed between phospholipid molecules and immobilises neighbouring hydrocarbon
chains, making the membrane more rigid.
Asymmetry of the lipid bilayer: the distribution of lipids between the inner and outer
layers is asymmetrical.
 1.3 Membrane lipid functions

Lipids determine the basic structure (bilayer) that is fundamental to the

organisation of all biological membranes.
They form an impermeable barrier to water-soluble molecules.
2- Membrane proteins

• They have an extracellular amino terminus (-NH2) and an intracellular

carboxyl terminus (COOH) and a hydrophobic body.
 2-1.Membrane proteins type
Depending on their location in relation to the lipid bilayer, two types of membrane
protein can be described:

A-Integral proteins (transmembrane or intramembrane) : cross the membrane from

one side to the other.

Their N-terminal domain often carries glycans located outside the plasma membrane.

The transmembrane (hydrophobic) domain consists only of apolar amino acid residues.
The hydrophilic parts are exposed to aqueous solutions on either side of the membrane.
• B-Peripheral, external or internal proteins or proteins associated
with an integral protein.
2-2. Membrane proteins properties

• A-Modes of organisation: Membrane proteins have two modes of

organisation, either integrated or peripheral.
• B-Fluidity: protein movements are less frequent, due to the large size
of these molecules compared with lipid molecules. They are slow and
mainly represent lateral diffusion movement within the lipid bilayer.
• C-Asymmetry: the distribution of plasma membrane proteins is
different on the two sides, which determines their role in relation to
the extracellular matrix (ECM) on the one hand and the cytoskeleton
on the other.
2-3. Main roles of membrane proteins

They act as:

• receptors and transporters (of matter or information),
• recognition and adhesion between cells attachment to neighbouring
cells or the extracellular matrix,
• capture of physical energy (light),
• enzymatic catalysts.
 3-Membrane carbohydrates
Cell membrane carbohydrates such as glycolipids, glycoproteins, and proteoglycans are
found on the outside surface of the cell to form the cell-coat.
Glycolipids: are membrane carbohydrates linked to lipids. These carbohydrate chains
help in cell-to-cell recognition.
Glycoproteins: are membrane carbohydrates linked to proteins. These compounds also
help with cell-to-cell recognition.
Proteoglycane: are long carbohydrate chains linked to a protein that is embedded in the
cell membrane. These structures regulate interactions between components in the cell
and communication between receptors. They also control the growth and production of
cells.
2-Glycocalyx functions
• Cell protection,
• Adhesion between neighbouring cells and/or between cell and
extracellular matrix,
• Cell specificity: marker for certain cells (e.g. blood group antigens),
• Recognition between cells for tissue organisation,
• Contact inhibition: controls cell division.
MEMBRANE TRANSPORT
The hydrophobic nature of the lipid double layer allows the cell to
maintain different concentrations of solutes on either side of the
membrane, i.e. between the cytoplasm and the extracellular
environment, and this is true for each cellular compartment
(mitochondria, lysosome, endoplasmic reticulum, etc.).

However, the compartments defined by the membrane do not have to

be completely separate, and molecular exchanges are necessary for
cell life.
Cells have developed systems for transporting ions and
macromolecules using membrane proteins: transporters,
pumps or channels.
Membrane transport is the passage of a molecule, ion or particle
through the phospholipid bilayer of the plasma membrane or
organelles. Membrane transport can take place :

Without membrane movement (passive or active transport)

With membrane movements (vesicular traffic).

Transport without membrane movements
 1-Passive transport
Molecules can cross the double layer by spontaneous movement towards equilibrium
without energy input, in the direction of the concentration gradient.

This is the movement of molecules from an area where they are in high concentration
to an area where they are in low concentration, so it assumes a concentration gradient:

a) Simple diffusion

b) Facilitated diffusion:

Transport through pores

Transporters or permeases
 1-Simple diffusion
This type of passage is only possible if the molecule is soluble in the
phospholipid membrane, i.e. if it can pass directly through the
phospholipid bilayer.

 The molecule must therefore be hydrophobic.

 Non-polar substances such as oxygen and waste products such as

CO2, urea and fats diffuse through the plasma membrane by
binding to its phospholipid compounds.
2-Facilitated diffusion
• This is always passive, but involves proteins.

• It is a specific and regulated phenomenon.

 A-Transport through pores

The pores that allow more specific ions to pass through are called ion channels
(Na+, cl-) whose transport takes place according to their electrochemical
gradient and does not require energy.
B-Transporters or permeases
• These are transmembrane proteins that bind the molecule to be
transported in a specific way. The "permease" changes conformation
and releases the molecule to be transported on the other side of the
membrane.
 2-Active transport
• A transport mechanism that involves the movement of molecules across the
membrane against the concentration gradient, meaning the transport of
substances from low to high concentration. This movement is achieved by
expending the energy of ATP (adenosine triphosphate).
• Two types of active transport are known:
a. Pumps (primary transporters)

• Use the energy from ATP hydrolysis to transport the molecule across
the plasma membrane (ATPases); for example :
• The concentration of Sodium ions on the
outside is greater than the concentration of
Sodium on the inside, so they should enter
the cell.
• The Sodium enters but is expelled to the
outside by the pump, which works using
energy from metabolism.
• For potassium ions, the opposite is true, i.e. they are pushed back into
the cell.

• The Ca++/ATPase pump

Same principle as the Sodium pump, it exists in the plasma membrane
of the endoplasmic reticulum.
 3- Secondary carriers (or co-transporters)

• These are transmembrane proteins which couple the passage of the

molecule with that of an ion (generally H+ and Na+):

the energy, which comes from moving the ion along its electrochemical
gradient, causes the other substance to move against its own gradient
(ATP is not used).

There are 3 types:

OTHER WAYS TO CROSS THE MEMBRANE
Some molecules (e.g. proteins) and particles are too large for
membrane transport.

Transporting these molecules therefore requires movement of the

plasma membrane to evacuate/ingestrate them:

Exocytosis

Endocytosis
 1-Endocytosis

Process by which a cell absorbs particles or solutes by enclosing them in

vesicles through invagination of the plasma membrane.
There are several types of endocytosis, depending on the substances
ingested and their size:
 Phagocytosis
 Pinocytosis
 Receptor-mediated endocytosis
 a) Phagocytosis
Phagocytosis is a type of endocytosis that involves uptake of large solid
particles, often >0.5 mm.
 b) Pinocytosis
Ingestion of suspended molecules taken from the extracellular
environment (e.g. lipid droplets). This is a frequent phenomenon in most
cells (especially kidneys and intestines).
 c) Receptor-mediated endocytosis

Selective endocytosis requires membrane receptors specific to the

molecule to be ingested.

The molecule/receptor complex is then endocytosed and localized in a

vesicle: the early endosome.
2-Exocytosis

Exocytosis is the process by which cells excrete waste and other large
molecules from the cytoplasm to the cell exterior and therefore is the
opposite of endocytosis.

There are two types of exocytosis:

Constitutive or renewal exocytosis

Regulated exocytosis
 a) Constitutive or renewal exocytosis
Exocytosis moves elements from the inside to the outside.
Constitutive exocytosis, which occurs in all cells, during which vesicles
continuously transport neo-synthesized molecules to the plasma membrane.
 b) Regulated exocytosis

Functions in specialized cells in response to a stimulus; example of

Ca+2 ion-induced exocytosis.
Intercellular Information Transmission
1-Hormonal information
• Although carried by the blood to all parts of the body, hormones only
act on specific target cells.
• They influence their targets by chemically binding to specific
receptors, which are proteins.
• Only the target cells of a hormone have the receptors to recognise and
bind to it.
• Two types of hormone are involved:
• Lipid-soluble hormones
• peptide hormones
a) Lipid-soluble hormone

• Iinclude steroid hormones, thyroid

hormones and nitric oxide (NO).

• These hormones are able to diffuse

across the membrane of the target cell
and directly produce a biological
response by acting on gene activity.
 b) peptide hormones :
• Include amino hormones, peptide hormones and protein hormones.
• As they are not fat-soluble, these hormones do not diffuse through the lipid
bilayer of the plasma membrane.
• Instead, these hormones bind to receptors from the surface of target cells.
• There, they act as a first messenger, triggering the production of a second
messenger inside the cell, where the specific hormonal responses take place.
Cyclic AMP (cAMP), which is synthesised from ATP, frequently serves as
the second messenger.
 2-Neurotransmission

• The presynaptic neuron releases neurotransmitter molecules by exocytosis

from the synaptic vesicles.
• After diffusing across the synaptic cleft, the neurotransmitter molecules
bind to receptors in the plasma membrane of the postsynaptic neuron,
generating a postsynaptic potential.
• As action potentials cannot cross the synaptic cleft, an indirect form of
communication is established there.
In general, chemical synapses function as follows:
• 1- The action potential arrives in a terminal bouton of a pre-synaptic axon.

2-The depolarisation phase of the action potential opens voltage-dependent Ca2+

channels in the terminal bouton membrane. Because they are more concentrated in
the interstitial fluid, calcium ions enter the terminal bouton via the open channels.

3- The increase in Ca2+ concentration inside the terminal bouton acts as a signal
that triggers the exocytosis of some synaptic vesicles, which release
neurotransmitter molecules into the synaptic cleft. Each synaptic vesicle contains
several thousand neurotransmitter molecules.
• 4- Neurotransmitter molecules diffuse across the synaptic cleft and bind to
neurotransmitter receptors located in the plasma membrane of the postsynaptic
neuron.

5- The binding of neurotransmitter molecules causes ion channels to open,

allowing certain ions to flow across the membrane.

6- The membrane voltage changes as the ions pass through the open channels.
This change in membrane voltage is a postsynaptic potential. Depending on the
type of ions passing through the channels, the postsynaptic potential may be a
depolarisation or hyperpolarisation of the postsynaptic membrane.

7- If it reaches the excitation threshold, the depolarising postsynaptic potential

triggers an action potential.
3-Neuromuscular junction (motor plate)

• A neuromuscular junction comprises the terminal boutons of a motor

neuron adjacent to the motor plate of a myocyte.

• When it produces an action potential (or nerve impulse), a motor

neuron triggers a muscle action potential in the myocytes to which it is
connected. What happens at a terminal button can be summarised as
follows.
• Release of acetylcholine: The arrival of the action potential at the terminal bouton
triggers the release of acetylcholine (ACh), the neurotransmitter contained in the
synaptic vesicles. ACh then diffuses into the synaptic gap between the motor
neuron and the motor plate.

• Activation of acetylcholine receptors: At the motor plate, ion channels are

inserted into the sarcolemma of the myocyte. ACh receptors are located on these
channels.

• Binding of ACh to the receptors opens the normally closed ion channel, allowing
small cations, mainly sodium ions (Na+), to pass through the membrane.
• Production of the muscle action potential: The arrival of Na+ in the myocyte triggers a
muscle action potential. Normally, each action potential gives rise to a muscle action
potential which propagates to the surface of the sarcolemma and inside the tubules.

• In response, the sarcoplasmic reticulum releases stored Ca2+ ions into the sarcoplasm.

• The diffusion of Ca2+ into the cytosol then causes the myocyte to contract.

• Degradation of Ach: The effect of ACh is short-lived because this neurotransmitter is

rapidly degraded in the synaptic cleft by an enzyme called acetylcholinesterase (AChE).