The document summarizes key aspects of cell membrane structure and function. It describes the fluid mosaic model of cell membranes, which views membranes as a fluid bilayer of phospholipids with embedded proteins. Membranes contain phospholipids, cholesterol, glycolipids, and integral and peripheral proteins. Transport across membranes is facilitated by both transporter proteins and channel proteins. Transport can occur through simple diffusion, facilitated diffusion, primary active transport using ATP hydrolysis, and secondary active transport coupling to the sodium-potassium pump. Membranes are selectively permeable and establish concentration gradients crucial for cell functions.

1. Internal Organization of the Cell
1

2. Introductory Questions
What is the structure of a cell membrane?
List functions of cell membrane.
What are the components of cell membrane?
What are membrane transport mechanisms?
2

3. Membrane Structure
Cell membranes are crucial to the life of the cell
Encloses the cell, defines its boundaries & maintains the
essential differences between the cytosol & the extracellular
environment
Membranes of organelles (inside eukaryotic cells), maintain
the characteristic differences between the contents of each
organelle and the cytosol
3

4.  Ion gradients across membranes, established by the activities
of specialized membrane proteins, can be used to;
Synthesize ATP,
Drive the transport of selected solutes across the membrane
Produce & transmit electrical signals (in nerve & muscle cells)
 In all cells, the plasma membrane also contains proteins that
act as sensors of external signals; e.g. receptors
4

5.  Cell membranes are dynamic, fluid structures
Common general structure: a very thin film of lipid & protein
molecules, held together mainly by noncovalent interactions
The lipid bilayer provides the basic fluid structure of the
membrane and serves as a relatively impermeable barrier to
the passage of most water-soluble molecules
5

6. Phospholipids are arranged in two layers; the phospholipid
head pointing outwards & the fatty acid tails inwards
This arrangement prevents polar molecules from crossing the
cell membrane, but hydrophobic molecules readily diffuse;
Phospholipids have relatively small hydrophilic head groups
The associations b/n the individual membrane lipids are
generally not very strong, giving most biomembranes a fluid-
like character
6

7. 7
The parts of a typical phospholipid molecule

8. 8

9. 9

10. The first model that attempted to describe the position of
proteins within the bilayer was proposed by Hugh Davson and
James Danielli in 1935
When viewed under a transmission electron microscope,
membranes exhibit a characteristic 'trilaminar’ appearance
Two layers of protein flanked a central phospholipid bilayer
Described as a 'lipo-protein sandwich’, as the lipid layer was
sandwiched between two protein layers
10

11. 11

12. Problems with the lipo-protein sandwich model:
It assumed all membranes were of a uniform thickness and
would have a constant lipid-protein ratio
It assumed all membranes would have symmetrical internal
and external surfaces (i.e. not bifacial)
It did not account for the permeability of certain substances
(did not recognize the need for hydrophilic pores)
The temperatures at which membranes solidified did not
correlate with those expected under the proposed model
12

13. A new model was proposed by Seymour Singer & Garth Nicolson in
1972
The fluid-mosaic model, remains the model preferred by scientists
today (with refinements)
13

14. Components of the Plasma Membrane
 Phospholipids: Phosphoglycerides & Sphingolipids
Form a bilayer with phosphate heads facing outwards & fatty
acid tails facing inwards; amphipathic/amphiphilic
Important for the fluidity of membrane, fluidity is crucial to
many membrane functions
14

15. Phosphoglycerides (glycerophospholipids):
Built from glycerol or they are esters of only two fatty acids,
phosphoric acid & glycerol; examples:
Phosphatidylcholine (PC or lecithin), phosphatidylethanolamine
(PE or cephalin), phosphatidylserine (PS), phosphatidylinositol
(PI, less abundant)
Sphingolipids: built from sphingosine (a long acyl chain with
an amino group (NH2) & two hydroxyl groups (OH) at one
end)
15

16. 16
Four major phospholipids in mammalian plasma membranes

17. 17
Phosphatidylinositol Diacylglycerol

18.  Cholesterol:
From the Ancient Greek chole – (bile) & stereos (solid), followed by
the chemical suffix –ol for an alcohol
It is a sterol/steroid (contains a rigid ring structure; reduces fluidity),
to which is attached a single polar hydroxyl group & a short
nonpolar hydrocarbon chain (contribute to fluidity)
Contributes to permeability to some solutes
Prevents the hydrocarbon chains from coming together and
crystallizing
Eukaryotic plasma membranes contain especially large amounts of
cholesterol – up to one molecule for every phospholipid molecule
18

19. 19

20. 20

21.  Glycolipids:
Lipids with a carbohydrate attached by a glycosidic (covalent)
bond
Found on the surface of all eukaryotic cell membranes, where
they extend from the phospholipid bilayer into the extracellular
environment
Based on the structure of the lipid moiety, they are generally
divided into two categories, glycosphingolipids (GSLs) &
glycoglycerolipids
21

22.  Functions of glycolipids:
Cell-cell interaction
Immune response
Facilitate cellular recognition (blood type)
Act as receptors for viruses & other pathogens to enter cells
22

23. 23
Glycolipid molecules

24.  Proteins:
According to their functions, they can be classified into three
classes: integral (transmembrane), peripheral & lipid-anchored
Integral proteins are permanently attached to the membrane
and are typically transmembrane (they span across the bilayer)
Peripheral proteins are temporarily attached by non-covalent
interactions and associate with one surface of the membrane
About 30% of the proteins encoded in an animal’s genome are
membrane proteins
24

25.  Structure of membrane proteins
The amino acids of a membrane protein are localized
according to polarity:
Non-polar (hydrophobic) amino acids associate directly with
the lipid bilayer
Polar (hydrophilic) amino acids are located internally and face
aqueous solutions
Transmembrane proteins typically adopt one of two tertiary
structures:
Single helices/helical bundles
Beta barrels (common in channel proteins) 25

26.  Functions of membrane proteins; they serve as:
Junctions: serve to connect & join two cells together
Enzymes: catalyze chemical reactions
Transporters: facilitated diffusion & active transport
Recognition: markers for cellular identification
Anchorage: attachment points for cytoskeleton & ECM
Transducers: receptors for peptide hormones
26

27. Membrane Transport of Small Molecules and
The Electrical Properties of Membranes
27

28. Lipid bilayers are virtually impermeable to most polar molecules
To transport small water-soluble molecules into or out of cells or
intracellular membrane-enclosed compartments;
Cell membranes contain various membrane transport proteins,
each of which is responsible for transferring a particular solute or
class of solutes across the membrane
Two classes of membrane transport proteins; transporters &
channels
Both form protein pathways across the lipid bilayer 28

29. Transporters (also called carriers, or permeases):
Bind the specific solute to be transported and
Undergo a series of conformational changes that alternately
expose solute-binding sites on one side of the membrane &
then on the other to transfer the solute across it
Channels: interact with the solute to be transported much
more weakly
Form continuous pores that extend across the lipid bilayer
29

30. Transport through transporters is either active or passive
Transport through channels is always passive (e.g. water
through aquaporins; osmosis)
Both active & passive ion transport is influenced by the ion’s
concentration gradient & the membrane potential that is, its
electrochemical gradient
30

31. 31

32. 32
Difference between channel proteins & carrier proteins

33. 33
The relative permeability of a synthetic
lipid bilayer to different classes of

34.  Simple Diffusion:
Passive process (no expenditure of ATP)
No utilization of carriers/channels
Movement of molecules from high to low concentration
Non-ionized &/lipid soluble substances can easily cross the cell
membrane
E.g.: respiratory gases (O2), waste product of aerobic respiration
(CO2), steroids hormones (e.g. testosterone, estrogen, vitamin D,
etc.), lipid soluble drugs
34

35.  The rate of diffusion is dependent on different factors
(especially for O2 & CO2)
Factors that  rate of diffusion:
Surface area, concentration gradient
Factors that  rate of diffusion:
Thickness of cell membrane, weight of the molecules
35

36.  Facilitated Diffusion:
Passive process that does not require energy (no ATP)
Movement of molecules from high to low concentration
Requires a channel or carrier protein; carries large & charged
molecules
Specific/selective & saturable process
E.g. movement of water molecules through aquaporins
36

37. Channel mediated facilitated diffusion
Types of channels for facilitated diffusion
All these allows charged molecules through them from an area
of high to low concentration, as they won’t be able to diffuse
through the cell membrane
 Leaky channels:
Usually found in neurons, K+ leaky channels are one of the
most important
It controls the resting membrane potential
37

38.  Voltage gated channels:
Important especially in neurons e.g. with Na+ & Ca2+ channels
A specific threshold needs to be reached for the channel to be
open & allow for Na+ & Ca2+ ions to go through the cell
Important in action potentials
38

39.  Ligand (or chemically) gated channels:
E.g. Na+ channels at the neuromuscular junction:
When ACh binds onto a binding site on the channel (nAChR), it
will open
Na+ will flow into the cell and generate an action potential that
will induce muscle contraction
39

40.  Mechanically gated channels:
Channels stimulated by mechanical stimuli (e.g. pressure)
Example:
If a finger got accidentally hit, this will open channels on the
pain receptors & allow ions to flow in (E.g. Na+)
As Na+ ions flow in, it will induce action potential
This activates pain receptors to send signal in the pain
pathway which will travel to the CNS mediated facilitated
diffusion
40

41.  Carrier mediated facilitated diffusion:
Example with Glucose:
Glucose molecules are carried through GLUT4 transporters (in
adipose & muscle tissue)
Insulin will stimulate the increases expression of GLUT 4 will
allow more glucose intake by the cell
41

42.  Primary Active Transport:
Directly uses ATP to move molecules from an area of low
concentration to a high concentration
Energy is needed to pump molecules against their gradient
ATP  ADP by ATPase; this creates energy
Examples:
Na+/K+ ATPase: transport 3 Na+ out & 2 K+ into the cell
Ca2+ ATPase: usually found in the SR of the muscle cells
H+/K+ ATPases (proton pumps): found mostly in the stomach
42

43.  Active transport is mediated by transporters coupled to an
energy source; ATP-driven pumps
ATP-driven pumps are often called transport ATPases because
they hydrolyze ATP to ADP and phosphate and use the energy
released to pump ions or other solutes across a membrane
There are three principal classes of ATP-driven pumps
43

44.  P-type pumps:
Structurally & functionally related multi-pass transmembrane
proteins
Called “P-type” because they phosphorylate themselves during
the pumping cycle
E.g. ion pumps responsible for setting up and maintaining
gradients of Na+, K+, H+ & Ca2+ across cell membranes
44

45.  ATP–binding cassette (ABC–transporters):
First discovered in cancer cells (MDR)
Differ structurally from P-type ATPases & primarily pump small
molecules across cell membranes
ATP act as a ligand
Phosphatidyl serine bind with T-subunit (if PS present in exoplasmic
phase)
Binding of ATP at A-subunit  conformation change then PS flipped
at cytoplasmic phase (E2-state)
45

46. Present on membrane of peroxisome, in human >48 ABC
transporter
In bacteria ~100 ABC transporter present
ABC-transporter has low specificity
ABC evolve for efflux of xenobiotics
ABC transporter act as Cl- channel in Cystic fibrosis
transmembrane conductance regulator (CFTR)
46

47.  Rotary ATPases:
Family of enzymes that are thought of as molecular
nanomotors
Classified in three types: F, A & V-type ATPases
F & A-type can synthesize & hydrolyze ATP, depending on the
energetic needs of the cell
V-type exhibits only a hydrolytic activity
47

48.  V-type pumps:
Turbine-like protein machines, constructed from multiple
different subunits
Structurally resemble with F-type pumps (similar)
Transfer H+ ions always against the concentration gradient
Always hydrolyze ATP, never act like ATP-synthase
48

49. First discovered in membrane of vacuole membrane
Present on lysosome, peroxisome, endosome, synaptic vesicles
& plant or yeast vacuoles (V = vacuolar)
Used to acidify the interior of these organelles
Responsible for acidification of endomembrane system (ER,
Golgi, endosome & lysosome)
49

50.  F-type ATPases (F0-F1 particle or ATP synthase):
Commonly called ATP synthases because they normally work
in reverse;
Instead of using ATP hydrolysis to drive H+ transport, they use
the H+ gradient across the membrane to drive the synthesis of
ATP from ADP & phosphate
Mainly located on plasma membrane of bacteria, inner
mitochondrial membrane, thylakoid membrane of chloroplast
50

51. 51

52. 52
Types Examples Location in the cell
P-type
(phosphorylation type)
Na+-K+ ATPase
Ca2+ ATPase
Plasma membrane
Sarcoplasmic reticulum
V-type (vacuolar type) H+-K+ ATPase Plasma membrane
F-type (energy
coupling factor)
ATP synthase Inner mitochondrial
membrane
ABC transporter CFTR proteins
MDR-1 protein
Plasma membrane
Plasma membrane
Summary

53. 53

54. 54

55.  Secondary Active Transport:
Indirectly uses ATP; depend on Na+/K+-ATPase (to generate ATP)
In this process, 2 types of molecules are involved; molecule X
which moves from an area of high to low conce. & molecule Y
moves from low to high concentration
Usually, molecule X is Na+ & molecule Y is glucose, H+, amino
acids, etc.
Na+/glucose co-transporter/symporter, Na+/K+/2Cl- symporter,
Na+/H+ antiporter, Na+/Ca2+ exchanger (antiporter)
55

56.  Vesicular transport:
Endocytosis
Pinocytosis: literally means “cellular drinking”
This occurs mostly in the intestinal cells
The cell creates a small invagination & absorbs the solutes &
water
The edges of the cell fuse together & buds the vesicle inwards
into the cell to create pinocytic vesicles
It will contain dissolved solutes and water
56

57. To move the vesicle deeper into the cell, the motor proteins in the
cytoplasm (kinesins & dyneins) bind onto the pinocytic vesicle and
move the vesicle
Releases water molecules and solutes into the cell that will be used
in metabolic processes
This is also an example of primary active transport
The motor proteins must use the energy derived from ATP binding &
hydrolysis to force a large movement in part of the protein molecule
57

58. Phagocytosis: literally means “cell eating”
This occurs mostly in white blood cells (especially, neutrophils
& macrophages)
The cell phagocytose mostly particle matter like pathogens
Actin molecule move into the cell membrane like arms called
pseudopods
The pseudopods buds off the cell & engulfs the particle matter
Two ends of the pseudopod come together and fuse
58

59. Actin molecules are also found in the end of the pseudopod to
pull the invaginated structure into the cell & form a vesicle
The vesicle is called phagosome
Protons are pumped into the phagosome to make the
environment acidic (because lysosomes have enzymes that
function better in acidic environments)
ATP is needed to pump protons into acidic environment
59

60. Phagosome joins with the lysosome in order to process the
pathogen to create a phagolysosome
Lysosomes contains hydrolytic enzymes that break down the
components of the pathogen
What remains after is secondary lysosome
Some of the remaining contents needs to be released from the
secondary lysosome and out of the cell
So the vesicle fuses with the cell membrane & releases the
remaining digested pieces of the pathogens via a process called
exocytosis
This process occurs so that the remaining can go through the
lymphatic and amplify the immune system
60

61. Receptor mediated endocytosis
This occurs mainly in the liver for the uptake of LDL
LDL receptor on the liver cell binds to LDL
Proteins called clathrin bind to the inner surface of cell
membrane and pull the membrane inward
This creates a pit clathrin coated pit
It will continue to be pulled inwards until it buds off to create a
vesicle
This is called an endosome
61

62. Outside the vesicle there will be clathrin, and inside there will
be the LDL receptors and the LDL molecules
Clathrin molecules will leave & proton pumps will appear on
the endosome
This will push protons into the endosome (via primary active
transport; with the use of ATP)
The protons are necessary as they weaken the bond between
the LDL receptor & LDL
62

63. Exocytosis
 Function:
Expel cellular waste
Mentioned in receptor mediated endocytosis & phagocytosis
Neurotransmitter release
Hormone release
Mucin produced by goblet cells
63

64. Mechanism of action of other processes
DNA is transcribed into mRNA in the nucleus
mRNA leaves the nucleus via the nuclear pores & binds to the
ribosomes
Ribosomes bind to the ER in order for translation to occur
mRNA translated into proteins  the protein molecule is
released in a vesicle
COPII, a signal protein, binds on to the vesicle & transports
the vesicle to the Golgi apparatus
Proteins undergo more modification
64

65. Then, protein is released in a vesicle from the Golgi apparatus
In its final form, it can be a hormone (e.g. insulin) or a
neurotransmitter (e.g. acetylcholine) or mucin
The vesicle is deep in the cell & needs to be moved to the cell
membrane
The microtubules in the cytoskeleton contain motor proteins
(dynein & kinesins), and they can transport the vesicle into the
cell membrane
The motor proteins utilize ATP to function (this is a primary
active transport process)
65

66. On the vesicle there are v-SNARE proteins & on the target cell
membrane there are t-SNARE proteins
These interact with one another and pull the vesicle to the cell
membrane until they fuse together
The contents of the vesicles are released out of the cell
v-SNARE & t-SNARE proteins are calcium dependent in order
to allow the process to occur
66