Cell Membrane

Dr.Annamalai.C
Physiology-Associate professor
Unisza kota kampus
 Learning objective
• Describe the typical cell membrane structure
and its components
• Explain the properties and functions of
membrane
• List some membrane disorders and their
clinical relevance
 Cell structure
Cell is the structural and functional Cell membrane
Cytoplasm
unit of the human body Nucleus
It is bound by cell
membrane(plasma membrane)
within which is enclosed the
protoplasm.

Protoplasm consists of
Nucleus- inner dense part
Cytoplasm- outer less
dense part
Nucleus is separated from the
cytoplasm by the nuclear
membrane
 Cell sturcture

• Cytoplasm consists of a fluid

base – cytosol, which contains
a number of organelles
 Basic cell membrane structure
• Cell membrane
7.5nm thick
• Basic framework is
made up double
layer of lipids
(predominantly
phospholipids)
suspended in an
aqueous medium
 Structure of phospholipid of cell
membrane
Each phospholipid molecule
is made up of an enlarged
head and two thin tails

The head(Polar end) –

contains phosphate portion. It
is hydrophilic in nature
(soluble in water)
The tail (non-polar end)–
made up of fatty acids. It is
hydrophobic in nature
(insoluble in water)
• The phospholipids are arranged in the aqueous cell membrane
in such a way that the heads of the 2 layers of phospholipids
face either sides of the cell membrane where as the
hydrophobic tails are hidden between the hydrophilic heads
• This arrangement gives the cell membrane a trilaminar
appearance with two densely stained layers separated by a
lighter stained zone
• On this bilaminar lipid layer suspended in an
an aqueous medium are interspersed protein
and carbohydrate moities giving the cell
membrane a fluid mosaic appearance
 Proteins in cell membrane
• Proteins of the cell membrane present as irregular masses
which are embedded within the thickness of the cell
membrane and project on one of its surfaces but a few may
project out of both of its surfaces and called as
transmembrane proteins
• Functions
a. Form an essential part of the structure of cell membrane –structural
protein
b. Some protein play a vital role in transport across the membrane and
act as pumps.
c. Few proteins form passive channels through which substances can
diffuse through the membrane
d. Act as receptors for specific hormones or neurotransmitters
e. Some proteins act as enzymes
 Carbohydrates of cell membrane
• The carbohydrate moieties are specially seen on the
external surface of the plasma membrane- forming a layer
referred to as the cell coat or glycocalyx layer
• The carbohydrates are attached to the proteins forming
glycoprotein or to lipids forming glycolipids

Outer surface
 Function of the glycocalyx layer
• This layer contains major histocompatibility
antigens ex. In erythrocytes it contains the
blood groups
• Most molecules of this layer are negatively
charged causing adjoining cells to repel from
each other and maintain an intercellular space
of 20nm
 Functions of cell membrane
a. Maintains shape of the cell
b. Controls the passage of substances into and out
of the cell
c. The cell membrane forms a sensory surface .
This is more developed in nerve and muscle
cells. The plasma membrane of such cells is
polarized so that the external surface is
positively charged and the internal surface is
negatively charged
d. The cell membrane bear receptors that are
specific for particular hormones or enzymes
 Cell contacts
• In tissues cells are closely packed so that cell
membranes of adjoining cells are separated from each
other by a narrow space of about 20nm.
• At certain places the cell membranes come into more
closer contact- cell contacts
• Classification of cell contacts
– Unspecialised contacts
– Specialised contacts(junctions)
• Anchoring junctions
– Adhesive spots(desmosomes)
– Adhesive belts
– Adhesive strips
• Occluding junctions(Tight junctions)
• Communicating junctions (gap junctions)
 Adhesive spots (Desmosomes)
• Most common type of
junction
• Present where strong
anchorage between cells
is needed
• At the site of the
desmosomes the plasma
membranes are
thickened and separated
from each other by a gap
of 25nm
• Example- Between cells
of the epidermis
 Occluding junctions (Tight junction)
• Occluding junctions are
seen typically near the
apices of epithelial cells
• At these junctions the
two plasma membranes
are in actual contact
• These junctions act as
barriers that prevent
movement of molecules
into intercellular spaces
 Communicating junctions(gap
junctions)
• At these junctions the
intercellular space is
reduced from the
normal 20nm to 3nm
• A minute canaliculus
connects the
cytoplasm of the two
adjoining cells allowing
for free passage of
substances between
adjoining cells
• These junctions are
widely distributed in
our body
 Cell organelles
• The cytoplasm of a typical cell contains
structures referred to as organelles. They
include
– Endoplasmic reticulum
– Ribosomes
– Mitochondria
– Golgi complex
– Various types of vesicles
– cytoskeleton
 Endoplasmic reticulum
• The cytoplasm of most cells
contain a system of membranes
forming the endoplasmic
reticulum
• These membranes are arranged
flattened sacs (cisterns)
• The presence of the
endoplasmic reticulum divides
the cytoplasm into the cytosol
outside the membranes and
vaculoplasm
• within the membranes
In most places the membrane
form the endoplasmic
reticulum(ER) is studded with
minute particles of RNA called
ribosomes
The presence of ribosomes gives
the membrane a rough
appearance therefore it is called
as the rough endoplamic
reticulum
Some membranes are devoid of
the ribosomes and have a smooth
appearance therefore called as
smooth endoplasmic reticulum
• Rough endoplasmic reticulum is the site of protein
synthesis
• The ribosomes attached it play a major role in this
• The lumen of the rough ER is continuous with
perinuclear space and on the other side it is continuous
with the lumen of the smooth ER
• The smooth ER is responsible for futher processing of
the proteins synthesised in the rough ER and synthesis
of lipids, especially phospholipids needed for the
formation of cell membrane
• Most cells have very little smooth ER, it is
predominantly seen in cells processing lipids
 Ribosomes
• Are seen in relation to
the ER but may also be
present free in the
cytoplasm
• They may be present
singly called
monosomes or in
groups called
polysomes
• Each ribosome consists
of a proteins and RNA
• They are essential for
protein synthesis
 Mitochondria(Mitos=granule
chondrium=rods)
• Appear as granules or rods
under the light microscope
• Greatest number of
mitochondria are seen in
cells with higher metabolic
activity
• The mitochondria are lined
by a smooth continuous
outter membrane and an
inner membrane which is
highly folded and forms
incomplete partitions
called as cristae
• The two membranes are
seperated by an
intermembranous space
• The space bounded by the inner membrane is
filled by a granular matrix containing numerous
enzymes, RNA and DNA
• The enzymes of the mitochondria play an
important role in the Kreb’s cycle
• The RNA and DNA enable the mitochondria to
divide
• The mitochondria are entirely maternal in origin
(derived from the fertilized ovum)
• ATP and GTP are formed in the mitochondria
from where they pass to other parts of the cell to
provide energy so mitochondria are referred to as
the power house of the cell
 Golgi Complex
• Golgi complex is made up of
membranes similar to those of
smooth ER
• The membranes form the walls
of a number of flattened sacs
that are stacked one over the
other
• Towards their margins the sacs
are continuous with small
rounded vesicles
• Functionally golgi complex is
divided into cis golgi close to
nuleus, trans goli close to cell
membrane and medial golgi in
between the two
• Material synthesised in the Smooth ER enters
into the cis golgi here some proteins are
phosphorylated and pass to medial golgi
• In the medial golgisugar residues are added to
the proteins and this passes to trans golgi
• In trans golgi proteolysis of some proteins
convert into active form, the various protiens
are sorted out and packed into approriate
vesicles(secretory vesicles, lysosomes)
 Membrane bound vesicles
• The cytoplasm of a cells may contain several
types of vesicles which are formed by the
budding off of existing areas of membrane.
• Some vesicles may store material,others
transport material in and out of the cell or
they may allow exchange of membrane
between different parts of a cell
 Different types of vesicles
• Phagosomes- vesicles
containing solid ingested
material
• Pinocytotic vesicles-
vesicles containing liquid
ingested material
• Exocytotic vesicles- vasicles
containing material which
is to be thrown out of the
cell
• Secretory granules- vesicles
seen in to contain granules
in secretory cells
• Storage vesicles- which
store lipid,s carbohydrates
etc.
• Lysosomes- vesicles containing enzymes which
destroy unwanted materials present within a
cell
• Peroxisomes- vesicles containing esnzymes
which react with substances to form hydrogen
peroxide which is used to detoxify various
substances by oxidation
 Cytoskeleton
• Cytoplasm is made up of a number of fibrillar
elements that collectively form a network
called as cytoskeleton
• Elements forming cytoskeleton into
– Microfilaments
– Microtubules
– Intermediate filaments
• Microfilaments- Are made up of protein actin. They are
seen to extend into cell projections like microvilli
• Microtubules- Made of protein tubulin. They are
formed in the centrioles
– They form the cytoskeleton
– Prevent the tubules of the ER from collapsing
– Some proteins present in membrane bound vesicles attach
themselves to microtubles and facilitate movement along
the tubules
– Form the mitotic spindles in a dividing cell
– Cilia contain microtubules
• Intermediate filaments- So called as they are
intermediate in size between the
microfilaments and microtubules
– They link cells together
– In the epithelium of the skin the filaments
undergo modification to form keratin. They form
the main constituents of hair and nail
– Form neurofilaments found in neurons
 Centrioles
• Two centrioles are seen as
two dots embedded in a
region of dense cytoplasm
called as centrosome
• The centrioles are seen as
two short cylinders that lie at
right angles to each other
• It consists of microtubules
arranged in the form of a
circle
• They play an important role in
cell division and form major
part of cell projections like
cilia flagella etc.
 Cell Projections
• Cilia

• Flagella

• Microvilli
CELL DIVISION
 MITOSIS
• Cell division occurring in normal cells or ‘Autosomes”.
• Each cell divides to give two daughter cells.
• The diploid number of chromosomes i.e., 44+ XY or
44+XX is maintained by replication of DNA.
• Each daughter cell has the same number of chromosomes as
the mother cell.
• Occurs in four stages.
 STAGES OF MITOSIS
• PROPHASE:
• The DNA content of the
chromosome is duplicated.
• The chromosome now
contains two identical
chromatids attached at the
centromere.
• The chromosomes then
gradually condense &
acquires a rod like
appearance.
 PROPHASE CONTD…..
• The two centrioles
move towards opposite
poles.
• They produce microtubules
to form spindle.
• The nuclear membrane starts
breaking down.
• The nucleolus disappears.
 METAPHASE

• Nuclear membrane has

completely disappeared.
• Spindle is fully formed.
• The chromosomes move
towards the centre of the
cell .
• They are attached to the
spindle at the centromeres.
 ANAPHASE
• The centromeres split
longitudinally so that
each chromatid gets
separated.
• They now form an
independent chromosome.
• The cell now has double
the amount of
chromosomes (46 pairs).
• The microtubules of the
spindle shortens pulling
the chromosome towards
the poles.
 TELOPHASE
• The nuclear membrane
reappears & forms two
daughter nuclei each with
23 pairs of chromosomes
(Diploid).
• The nucleolus reappears.
• The chromosomes gradually
become uncoiled.
• This is followed by division
of cytoplasm wherein two
identical daughter cells are
formed.
 TELOPHASE
• Two identical daughter cells
formed will have diploid
number of chromosomes as
their mother cells.
• The cell membrane is formed.
 MEIOSIS
• Occurs only in Gametes (sperms & ova).
• Has two successive divisions –
Meiosis-I & Meiosis- II.
• The first meiotic division is a reduction division.
• The Diploid number of chromosome is halved to
Haploid number of chromosomes.
• When two gametes with haploid no. of
chromosomes(23) fuse the diploid number of
chromosomes(46) is maintained.
 FIRST MEIOTIC DIVISION

PROPHASE
• Divided into four stages
• Leptotene
• Zygotene
• Pachytene
• Diplotene
 LEPTOTENE
• Duplication of DNA
content
• Chromosomes condense &
become visible
• Two chromatids are attached
to each centromeres
• However the chromatids
cannot be clearly
distinguished
 ZYGOTENE
• Two homologus chromosomes
align themselves close to each
other – these constitute a
bivalent
• One out of each homologus
pair is inherited from each
parent.
• This pairing is called synapsis
or conjugation
• Each pair come to lie in the
middle of the spindle.
 PACHYTENE
• Two chromatids become
distinct.
• Each bivalent now has four
chromatids - Tetrad
• Two central & two peripheral
chromatids.
• Two central chromatids become
coiled around each other &
cross over at 30 – 40 points.
• Site where chromatids cross are
adherent –CHIASMATA.
 DIPLOTENE
• With the contraction of
spindle the the chromosomes
of each pair move towards
opposite poles.
• The chromatids involved in
crossing over break & loose
pieces become attached to
opposite chromatids.
• There is thorough shuffling
of genetic material.
• Each cell produced have
distinct genetic content.
 METAPHASE

• All 46 chromosomes
become attached to the
spindle at the equator.
 ANAPHASE
• One entire chromosome of
each homologus pair with
two chromatids separate &
move towards opposite
poles – DISJUNCTION

• There is no splitting of the

centromeres.
• The chromosome number
becomes halved – Haploid.
 TELOPHASE
• The nuclear membrane is
formed .
• Followed by division of
cytoplasm.
• Two daughter cells with
haploid no. of
chromosomes(23) are
formed.
 SECOND MEIOTIC DIVISION
• Similar to mitosis
• First meiotic division is followed by a short
interphase
• There is no duplication of DNA, because
duplication has already occurred during
Meiosis – I.
• Each chromosome splits at centromere &
chromatids are drawn towards opposite poles.
• The resultant daughter cells are not identical in
their genetic content.
 IMPORTANCE OF
MEIOSIS
• Provides constancy of chromosome number.

• When two gametes with haploid no. of chromosomes fuse

the diploid no. of chromosomes is maintained in the
resultant daughter cells.

• Random assortment of maternal & paternal chromosomes

• Shuffling & recombination of genetic material.

 CHROMOSOMAL ABNORMALITIES
• May originate during meiosis or mitosis.
• Haploid – 23 chromosomes (22 autosomes & 1 sex
chromosome)
• Euploid – Multiples of haploid. Eg:
• Diploid – (23x2) 46 chromosomes ( 22 pairs of autosomes
& 2 sex chromosomes)
• Triploid – (23x3) = 69 chromosomes (66autosomes & 3
sex chromosomes)
• Aneuploid – Any one chromosome number that is not Euploid.

• Trisomy : When an extra chromosome is present involving a

particular pair.(Total - 47)

• Tetrasomy : When two extra chromosomes are present in a

pair.(Total - 48)

• Monosomy : One chromosome is less in a pair.(Total - 45)

 NONDISJUNCTION
• During Meiosis I homologus pairs with two chromatids
separate & move towards opposite poles.
• Instead, if both of them move towards same pole –
Nondisjunction.
• One cell will get one chromosome extra – Trisomy eg:
Trisomy 21,18,13 etc.
• One cell will get one chromosome less – Monosomy.eg:
Turner’s syndrome 45,XO
• May involve autosomes or sex chromosomes
NON DISJUNCTION
 TRANSLOCATION
• Sometimes during separation in Meiosis - I some
chromosome parts break & attach to chromosome of
adjacent or another pair at the point of attachment of
chiasma.

• Such translocations lead to altered phenotype.

• More common between 13,14,15,21 & 22 chromosomes.

Transport across membrane
Physiological
activities
of cell
depends on
membrane
transport.
 Functions of the Plasma Membrane
1. Isolation – Selective, from environment
2. Regulation – Exchange of essential substances.
3. Communication – with other cells
Structure of the Plasma Membrane
A- Phospholipid bilayer
B - Cholesterol
C - Proteins.
D - Carbohydrates.
Phospholipid bilayer – Functional
significance - Semi-permeablity

Hydrophobic
 Permeable and nonpermeable substances across
plasma membrane
Permeable
1. Non polar, lipid soluble-
Fattyacids, glycerol, steriod ,
Vit A,D,E,K and O₂,CO₂,N₂
2. Small polar molecules like
H2O and urea.
Nonpermeable
1. Large polar molecules like
glucose and aminoacid
2. Ions

Not all substances can pass through a cell membrane

 Plasma proteins
Proteins floating in the phospholipid bilayer.
Types of proteins
1. Peripheral proteins , present on the surface of the
membrane.
2. Integral proteins, extend into and sometimes
completely through the membrane.
Integral proteins:
a. Marker or Recognition proteins,
b. Transport proteins,
c. Receptor proteins.
Methods of Transport Across Membranes
1. Passive Transport
2. Active Transport
3. Vesicular transport

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 1.Passive Transport

1. Mechanism of transport of substance along the

gradient without expenditure of energy.
2. Depends on physical factors.
3. It’s a downhill movement
[HI] [LOW]
4. Two types
a) Diffusion
b) Osmosis
 1.Diffusion
Passive transport of molecules from area of higher
concentration to the area of lower concentration.

Types of Diffusion
(a) Simple diffusion
(b) Facilitated diffusion

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 1.Diffusion
a) Simple diffusion
Movement of atoms or molecules
from a higher concentration to low
concentration due to random
movement.
Depends on various physical
factors.
(Fick’s law of Diffusion)
Ceases at Diffusional equilibrium.
Factors Influencing rate of diffusion – Fick’s law

R=DA (P/d)
D- Diffusion Coefficient

P X A X S
Dα
d X √ MW

1. Concentration gradient (P- C1 and C2= concentration of S on

each side of membrane)

2. Electrical , pressure gradient

3. Membrane Thickness (d- distance diffusion path length)
4. Membrane Surface area(A)
5. Lipid Solubility (S)
6. Molecular wt (MW)
 Types of Simple Diffusion
1) Simple diffusion of lipid soluble substance.
2) Diffusion of water.
3) Simple diffusion of lipid insoluble substance
through protein channels.

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 Types of Simple Diffusion
1) Simple diffusion of lipid soluble substance

Rate of diffusion α lipid

solubility of the substance.
Lipid soluble diffuse
veryrapidly through the lipid
bilayer.
Examples:
O₂, N₂, CO₂, alcohol, steroid
hormones ,weak acids and bases

Savitha Niren 30/06/2012

 Types of Simple Diffusion
2) Diffusion of water
Water, a lipid insoluble
substance can pass through the
cell membrane.
Transmembrane protein
channels - Aquaporins

Savitha Niren 30/06/2012

 Types of Simple Diffusion
3) Simple diffusion of lipid insoluble substance
through protein channels.
Protein channels are tube
shaped channels which extend
from the extracellular to
intracellular ends.
Permeability depends upon
the size, shape and charge.

Savitha Niren 30/06/2012

2.Simple diffusion of lipid insoluble substance
through protein channels

Savitha Niren 30/06/2012

 Selective permeability

Protein channels
Tube shaped channels. - - -
Two important characteristics - -
- -
a) Selective permeability
b) Gating mechanism
1. Voltage gated channels
2. Ligand gated channels
3. Mechanical gated channels

Savitha Niren 30/06/2012

 b) Gating mechanism
1.Voltage gated channels

Respond to the electrical potential

across the cell membrane.
Patch clamp technique to study the activity of
ion channels
 b) Gating mechanism
2.Ligand or chemical gated channels
Ligand
Protein channel gates are opened by
the binding of a chemical
substance(ligand) with the protein
and cause a conformational
change in the protein molecules.
Eg : Ach receptor
 b) Gating mechanism
2.Ligand gated channels
Types of Ligand binding
a)External or extra cellular b) Internal or intra cellular
Ligands Ligands -Second messengers
Eg: Ach channels Eg: cAMP

Savitha Niren 30/06/2012

 b) Gating mechanism
3.Mechanical gated channels
Protein(mechanosensitive) channels are
opened by mechanical stimuli like stretch.
Eg: K⁺ channels in hair cell.

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Facilitated transport or Carrier-mediated
transport
Diffusion of water soluble
large molecules across the
cell membrane with the help
of carrier proteins.
Here the rate of diffusion
approaches a maximum
level, Vmax.

Examples: Glucose
b) Mechanism of Facilitated Diffusion

Binding of the molecule to the

receptor site in the carrier
protein.

Binding initiates
a conformational change

This allows the diffusion of the

molecule
b) Facilitated Diffusion
 Types of Carrier proteins
1. Uniporter- transports only one type of molecule.
2. Symporter- coupled transport of 2 different molecules in
the same direction. Eg. Transport of Na⁺/glucose in renal tubule
3. Antiporter- coupled transport of 2 different molecules in
the opposite direction.
Eg. Exchange of Na⁺ and H⁺ in renal tubule
 Difference between simple and facilitated diffusion
1. Specificity – Carrier proteins are highly specific for different
molecules.
2. Saturation – In SD rate of diffusion α conc. of the substance and
there is no limit.
- In FD there is saturation point – all the binding sites on the
carrier proteins are occupied.
3. Competitive inhibition – When A and B are transported by the
same carrier.
 Factors affecting net rate of diffusion
1.Cell membrane permeability(P)
Thickness of the membrane.
Lipid solubility
Distributionof protein channels in the cell memb.
Temperature
Size of the molecules
Area of the membrane.
Diffusion coefficient D=PxA.
2. Concentration gradient:
Net diffusion αD (C0-C1)
3. Electrical potential gradient( is the combined effect conc. Gradient & electrical
potential gradient)
At normal body temp (37°C), the electrical gradient that will balance the
concentration gradient of a univalent ion can be determined by Nernst
equation EMF = 61 Log C0/C1.
4. Pressure gradient:
 2.Osmosis
The diffusion of water from an area of high
concentration of water molecules to an area of low
concentration of water across a semi permeable
membrane.

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 Osmotic pressure
Minimum pressure per
unit area which is
applied on the side of
higher concentration to
prevent osmosis.
Osmotic pressure
exerted by colloidal
substance in the body
is called colloid osmotic
pressure.
Plasma proteins -
Oncotic pressure.
Significance ??
Savitha Niren 30/06/2012
Osmosis - Moles vs Osmoles
Mole
mole = 6.022 x 1023 particles of solute
One Osmole is equal to one mole of
osmotically active particles of solute
particles.
Osmoles – Total no of particles in the
solution is measured in terms of
osmoles.
– Example one mole of NaCl = 2 osmoles of
osmotically active particles.
Osmolality vs osmolarity

Osmolality
Osmolality = # moles / kg of solution

Osmolarity
Osmolarity = # moles / L of solution
Importance of number of Osmotic particles (or
of Molar concentration) in determining
Osmotic pressure.
The osmotic pressure
exerted by particles in a
solution, whether they are
molecules or ions, is
determined by the number
of particles per unit volume
of fluid and not by the mass
of the particles.

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 Tonicity
1. Isotonic : Same concentrations on both
sides of the membrane
2. Hypotonic : Less concentration than the
other side.
3. Hypertonic : More concentrated than the
other side.
Solutions – isotonic to plasma??
 Osmotic equilibrium between intracellular
& extracellular fluid

RBCs in Isotonic solution RBCs in Hypotonic solution

Savitha Niren 30/06/2012

RBCs in Hypertonic solution
 Applied aspects of osmosis
1. Severe dehydration – may increase plasma osmolality.
2. In severe diabetes – increased blood glucose -
increase plasma osmolality.
3. Excessive intravenous administration of 5% glucose
decreases plasma osmolality leading to swelling of
the body tissues.
4. Hyperosmolality causes coma(brain cells)
hyperosmolar coma.
5. In renal diseases – plasma urea level increases and
causes hyperosmolality.
 References

• Textbook of Medical physiology-AC

Guyton
• Review of medical physiology-WF
Ganong