1. CELL MEMBRANE

2. At the end of this class you
will know about…
• Detailed structure of plasma membrane
• Variants of cell membrane
• Clinical implications
• Transport across the membrane

3. Cell (plasma) membrane
• Cells need an inside & an outside…
– separate cell from its environment
– cell membrane is the boundary
IN
Food
Sugars
Proteins
fats
salts
O2
H2O
OUT
waste
- ammonia
- salts
- CO2
- H2O
products
- proteins
cell needs materials in & products or waste out

4. Other functions
• Selectively permeable
• Exchange of materials- endocytosis/ Exocytosis
• Cell-cell interaction
• Transmembrane signaling
• Support
• Protection
• Controls movement of materials in/out of cell
• Ectoenzymes- secretory function
• Barrier between cell and its environment- ~8nm thick
• Maintains homeostasis

5. Comparison of mean conc of various
molecules outside and inside of a cell

6. Fluid Mosaic model of membrane
It is fluid, it is mosaic in pattern

7. Singer & Nicolson (1972) gave the
structure of fluid mosaic model
• Davson & Danielle gave the lipid bilayer
structure
• Singer & Nicolson proposed that membrane
proteins are integrated too

8. Characteristics of plasma
membrane
• 7-10 nm thick
• Phospholipids are arranged
in bilayer
• Polar heads towards
extracellular side &
cytoplasmic side
• Hydrophobic interior

9. Phospholipid bilayer
polar
hydrophilic
heads
nonpolar
hydrophobic
tails
polar
hydrophilic
heads

10. Icebergs floating in the sea~
Transmembrane proteins floating in the sea
of PL
• Choline containing PL- external layer
• Ethanolamine & Ser containing PL – internal
layer
• Each leaflet- 25A0
• Head portion- 10A0
• Tail - 15A0
• Free lateral movement in lipid layer- Fluidity
of the membrane
• Flip-flop movement restricted

11. Flip-flop movement only during apoptosis!-
enzyme catalyzed process
• Flippases- Transfer of amino
phospholipids across the membrane
• Floppases- catalyze outward directed
movement expending ATP

12. Factors affecting fluidity of
membrane
• ↑Saturated FA- rigidity
• ↑ Unsaturated FA- fluidity
• Cis double bond in hydrocarbon
chain- ↑ fluidity
• ↑Temperature – disordered state,
↑ fluidity
• Cholesterol- below Tm ↑ fluidity
- beyond Tm ↓fluidity
• ROS, ↑cytosolic Ca,
anaesthetics- adversely affect
fluidity

13. Membrane Lipids
• Glycerophospholipids, sphingolipids &
cholesterol
• Lipid: protein mass ratio 1:4- 4:1
• Non-covalent interactions hold proteins
and lipids
• Glycerophospholipids, sphingolipids-
major lipid

14. Membrane proteins
Peripheral proteins - on surface
Bound to lipids by electrostatic & H-bond
interactions with the head groups of lipids
Integral proteins- Interact extensively with
hydrocarbon chains of membrane lipids
• Proteins are firmly anchored by covalent
linkages--- GPI (Glycosyl phosphatidyl inositol)
anchor

15. • Transmembrane proteins-
span the whole bilayer
Hydrophobic side chains
embedded in the
hydrophobic central core
Serve as receptors, tissue
specific antigens, ion
channels, membrane-based
enzymes

16. Many Functions of Membrane Proteins
Outside
Plasma
membrane
Inside
Transporter Cell surface
receptor
Enzyme
activity
Cell surface
identity marker
Attachment to the
cytoskeleton
Cell adhesion

17. Membrane carbohydrates
• Play a key role in cell-cell recognition
– ability of a cell to distinguish one cell from
another
• antigens
– important in organ &
tissue development
– basis for rejection of
foreign cells by
immune system

18. Different bonds are involved
A. Covalent bond-
Peptide bonds
Disulfide bond
Lysinonorleucine bond
B. Non- covalent bond
Hydrogen bond
Hydrophobic interaction
Electrostatic/ ionic bond/salt bridges
Van der Waal’s interactions

19. Hydrophobic bonds
• Interaction between non-polar hydrophobic R
groups of amino acids like Ala, Val, Leu, Ile,
Met, Phe & Trp
Ionic bonds
• Between oppositely charged groups
Van der Waal’s interactions
• Extremely weak- attractive force between
chemical groups in contact
• Act at a very short distance

20. Specialized membrane
structures
• Tight junction- certain places instead of 4
layers 3 layers are seen- claudin, occludin,
junctional adhesion molecule
• Helps in cell communication
Lack of tight junction- cancer metastasis due
to loss of contact inhibition
• Myelin sheath
• Microvilli
• membranes of organelle
• Cytoskeleton & molecular motors

21. Ratio of protein to lipid in
different membranes

22. “The life so short, the craft so long to
learn. ”
― Hippocrates

23. TRANSPORT MECHANISMS

24. Permeability across membrane-
depends on solubility in lipids
Cell membrane transport
Passive transport Active transport Pumps
Simple diffusion Facilitated
diffusion
Ion channels

25. 1.Diffusion- movement from high to
low concentration
2nd law of thermodynamics governs the system:
Universe tends towards disorder (Entropy)
• No energy required

26. AS Biology, Cell membranes and
Transport
26
Molecules that diffuse through
cell membranes
1. Oxygen – Non-
polar so diffuses
very quickly.
2. Carbon dioxide –
Polar but very
small so diffuses
quickly.
3. Water – Polar but
also very small so
diffuses quickly.

27. 2. Facilitated diffusion
Carrier-mediated process
Carrier mechanism can be saturated
Structurally similar molecules compete
Operates bi-directionally
No energy required, but faster than
simple diffusion
Exist in 2 conformations- Ping & Pong

28. A passive
process
• Large polar
molecules such as
glucose and
amino acids,
cannot diffuse
across the
phospholipid
bilayer. Also ions
such as Na+ or Cl-
cannot pass.

30. Simple vs. facilitated diffusion
inside cell
outside cell
lipid
inside cell
outside cell
H2O
simple diffusion facilitated diffusion
H2O
protein channel

31. Aquaporins
• Channels for water molecule
• At least 11 are there
• Form tetramers in the cell membrane
Clinical significance:
Nephrogenic DM
Channelopathies- Cystic fibrosis
(Cl- channel), Liddle’s syndrome
(Na+ channel), periodic paralysis (K+
channel)

32. 3. Ion channels
Transmembrane proteins
Selective for one particular ion
Regulation of activity- voltage-gated,
ligand-gated or mechanical-gated
Transport is very fast
Mainly for electrolytes like Na+, K+, Cl-
& Ca++
Transport down the gradient

33. Ligand-gated ion channels
• Binding of a ligand to a receptor site on
the channel opens/closes the channel
• Ach receptor- Ach after released binds
to the post-synaptic region– allows
influx of Na+-- action potential– channel
opens

35. Clinical significance
• Sodium channels- local anaesthetics,
Liddle’s disease
• Potassium channels- mutation leads to
“Long QT syndrome”
• Chloride channels – Cystic fibrosis
• Retina- light induced hyperpolarization of
the retinal membrane

36. Ionophores
1. Mobile ion carriers- Valinomycin
2. Channel formers- gramicidin
ion gradient is dissipated- behave as
uncouplers of ETC

37. Active transport
• Requires energy
• Against conc. gradient
• Active transport is unidirectional
• Requires specialized integral
proteins- Transporters
• Transport system is saturated at
higher concentration of solutes
• Transporters are susceptible to
inhibition

38. …..Active transport
• Cells may need
molecules to move
against
concentration “hill”
– need to pump “uphill”
• from LOW to HIGH
using energy
– protein pump
– requires energy
• ATP
ATP

39. Pumps
• Na+ K+ ATPase / sodium pump
• Calcium pump- sarcoplasmic reticulum in
skeletal mm.

41. Different transport systems
Uniport- Single solute across the membrane e.g.
glucose transporter
Co-transport- Transfer of one molecule depends on
simultaneous or sequential transfer of another
molecule, energy may be involved indirectly
 Symport- carries both the molecules in same
direction; Ex- Sodium-dependent glucose transport
 Antiport- Opposite direction; Ex- Cl- HCO3
- exchange
across RBC, sodium pump

42. Symport Vs Antiport

43. Clinical significance
• Hartnup’s disease
• Cystinuria
• Vit D resistant rickets

44. How about large molecules?
• Moving large molecules
into & out of cell
– through vesicles & vacuoles
– endocytosis
• phagocytosis = “cellular
eating”
• pinocytosis = “cellular
drinking”
– exocytosis
exocytosis

45. Endocytosis
Phagocytosis
Pinocytosis
Receptor-mediated
endocytosis
fuse with
lysosome for
digestion
non-specific
process
triggered by
molecular signal

46. It is the darkest before daw
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