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Lecture 3 Cell Membrane

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DOI: 10.13140/RG.2.2.33526.96327

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 Lecture 3
Dr. Mohamed Kotb El-Sayed
Associate Professor of Pharmaceutical Biochemistry & Molecular Biology

1
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Objectives CELL MEMB.

By the end of this lecture you should be familiar with:

 Describe the different membrane structure models.

 Describe the structure of plasma membrane and state its function.

 Identify the components of plasma membrane.

 Identify types of proteins, lipids and carbohydrates in the membrane.

 Describe bilayer arrangement and membrane asymmetry.

 Explain the functions of different membrane proteins.

 Explain the functions of different membrane lipids and carbohydrates.

 Explain the membrane fluidity.

2
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Cell Wall vs. Cell Membrane CELL MEMB.

 All living cells have cell membranes (plasma membrane).

 Cell wall is most found in plant cells.

 Remove cell wall under appropriate conditions and cell lives. However

minor disruption of cell membrane  cell death.

 Plasma membranes are selectively permeable that separate the interior of
the cell from the environment.
 Cell membranes contain lipids and proteins that form their structure and
facilitate cellular function. E.g., cell adhesion and cell signaling are cellular
processes initiated by the plasma membrane.
 Plasma membranes also serve as attachment points for intracellular
cytoskeletal proteins.
3
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
How does the Cell Membrane Look Like? CELL MEMB.

 They cannot see it….But they could make observations and

deductions:
1-Observation:
 Lipid and lipid soluble materials enter cells more rapidly than
substances that are insoluble in lipids.
Deductions
 Membranes are made of lipids.
 Fat-soluble substance move through the membrane by dissolving in it
("like dissolves like").
2-Observation:
 Phospholipids are Amphipathic: molecule has both a hydrophilic
region and a hydrophobic region.
 Phospholipids will form an artificial membrane on the surface of water
4 with only the hydrophilic heads immersed in water.
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
How does the Cell Membrane Look Like? CELL MEMB.

Deductions:
 Because of their molecular structure,
phospholipids can form membranes.
3-Observation:
 Phospholipid content of membranes
isolated from red blood cells is just
enough to cover the cells with two layers.
 Membranes isolated from red blood cells
contain proteins as well as lipids
Deductions:
 Cell membranes are phospholipid
bilayer, two molecules thick.
 There is protein in biological
membranes.
5
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Components of Cell Membrane CELL MEMB.

 The major components of all cellular membranes are lipids and proteins.
 Lower concentration of carbohydrates are present.

6
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Danielli and Davson Model CELL MEMB.

 Cell membrane is made of a phospholipid bilayer sandwiched

between two layers of globular protein.
 The polar (hydrophilic) heads of phospholipids are oriented towards
the protein layers forming a hydrophilic zone.
 The nonpolar (hydrophobic) tails of phospholipids are oriented in
between polar heads forming a hydrophobic zone.

7
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Problems with the Danielli and Davson CELL MEMB.

 Not all membranes are identical or symmetrical.

 Membranes with different functions also differ in chemical composition
and structure.
 Membranes are bifacial with distinct inside and outside faces.
 A membrane with an outside layer of proteins would be an unstable
structure.
 Membrane proteins are not soluble in water, and, like phospholipid,
they are amphipathic.
 Protein layer not likely because its hydrophobic regions would be in an
aqueous environment, and it would also separate the hydrophilic
phospholipid heads from water.
8
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
The Fluid Mosaic Model CELL MEMB.

 It was proposed by Singer & Nicolson (1972).

 It is the model that is currently accepted.

 “The biological membranes can be considered as a two-dimensional liquid where

all lipid and protein molecules diffuse more or less freely” .
 The membrane has 2 major molecular components:

Lipids = mostly phospholipids & cholesterol.

Proteins =
A. Integral (intrinsic).

B. Peripheral (extrinsic).

9
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
The Fluid Mosaic Model CELL MEMB.

 The membrane is described as a fluid, owing to the ability of lipids to diffuse

laterally within the plane of the membrane.
 The overall structure is likened to a flowing sea. And, like a mosaic,
membrane proteins are dispersed throughout the membrane.
 Many of the membrane proteins retain the ability to undergo lateral motion

and are likened to icebergs floating within the sea of lipids.

10
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Lipids CELL MEMB.

 They are the most abundant type of macromolecule present (40% and
80%).
 Provide both the basic structure and the framework of the membrane and
regulate its function.
 Three types of lipids are found in cell membranes: phospholipids,
cholesterol, and glycolipids.
1. Phospholipids:
 The most abundant of the membrane lipids.
 They are polar, ionic compounds that are amphipathic in nature. That is,
each has a hydrophilic head, which is the phosphate group plus whatever
alcohol is attached to it (for example, serine, ethanolamine, and choline)

11
and a long, hydrophobic tail containing fatty acids.
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Lipids CELL MEMB.

 While the polar head groups of the outer leaflet

extend outward toward the environment, the fatty
acid tails extend inward.
 The basic structure of cell membranes is a
phospholipid bilayer. Two antiparallel sheets of
phospholipids form the membrane that surrounds the
contents of the cell.
 The layer closest to the cytosol is the inner leaflet
while the layer closest to the exterior environment is
the outer leaflet.
 Phospholipids that present in the plasma membrane:
A. Glycerol PL  Phospholipids contain glycerol. E.g.:
phosphatidylserine, phosphatidylethanolamine,
phosphatidylinositol, and phosphatidylcholine.
B. Sphingo PL  Phospholipids contain sphingosine.
12 E.g.: sphingomyelin.
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Lipids CELL MEMB.

13
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Lipids CELL MEMB.

2. Cholesterol
 An amphipathic molecule, cholesterol contains a
polar hydroxyl group as well as a hydrophobic steroid
ring and attached hydrocarbon.
 It is dispersed throughout cell membranes,
intercalating between phospholipids. Its polar
hydroxyl group is near the polar head groups of the
phospholipids while the steroid ring and hydrocarbon
tails of cholesterol are oriented parallel to those of
the phospholipids.
 It fits into the spaces created by the kinks of the
unsaturated fatty acid tails, decreasing the ability of
the fatty acids to undergo motion and therefore
causing stiffening and strengthening of the
14membrane.
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Lipids CELL MEMB.

3. Glycolipids:
 Lipids with attached carbohydrate (sugars), glycolipids are found in
cell membranes in lower concentration than phospholipids and
cholesterol.
 The carbohydrate portion is always oriented toward the outside of the
cell, projecting into the environment.
 Glycolipids help to form the carbohydrate coat observed on cells and
are involved in cell-to-cell interactions.
 They are a source of blood group antigens and can act as receptors for
toxins including those from cholera and tetanus.
15
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Proteins CELL MEMB.

 Proteins are largely responsible for many biological functions of the

membrane. For example, some membrane proteins function in transport of
materials into and out of cells. Others serve as receptors for hormones.
 The types of proteins within a plasma membrane vary depending on the cell
type. However, all membrane proteins are associated with membrane in one
of three main ways.

16
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Association Proteins CELL MEMB.

1- Integral proteins:
 They are inserted into membrane, so their hydrophobic regions are
surrounded by hydrocarbon portions of phospholipids.They may be:
 Unilateral, reaching only part way across the membrane.
 Transmembrane, with hydrophobic midsections between hydrophilic
ends exposed on both sides.
 These proteins are oriented with their hydrophilic portions in contact
with the aqueous exterior environment and with the cytosol and their
hydrophobic portions in contact with the fatty acid tails of the
phospholipids.

17
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Proteins CELL MEMB.

1- Integral proteins:
 Integral proteins are difficult to remove from membrane.

 You must use detergents to dissolve integral membrane away.

 The membrane is destroyed while extracting integral proteins.

2- Peripheral proteins:
 They are not embedded but attached to the membrane's surface.

 May be attached to integral proteins.

 On cytoplasmic side, may be held by filaments of cytoskeleton.

 They are easy to remove from membrane when treated with high salt and
the membrane is not destroyed.
 Such as those involved in the spectrin membrane skeleton of erythrocytes.
18
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Proteins CELL MEMB.

3. Lipid-anchored proteins:
 They are attached covalently to a portion of a lipid without entering the
core portion of the bilayer of the membrane.
 Both transmembrane and lipid-anchored proteins are integral membrane
proteins since they can only be removed from a membrane by disrupting
the entire membrane structure.

19
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Proteins Functions CELL MEMB.

20
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Functions of Membrane Proteins CELL MEMB.

1-Transport:
 (a) A protein that spans the membrane may provide a
hydrophilic channel across the membrane that is selective for
a solute.
 (b) Other transport proteins shuttle a substance from one
side to the other by changing shape. Some of these proteins
hydrolyze ATP as an energy source to actively pump
substances across the membrane.
2-Enzymatic activity:
 A peripheral protein built into the membrane may be an
enzyme with its active site exposed to substances in the
adjacent solution. In some cases, several enzymes in a
membrane are organized as a team that carries out sequential
steps of a metabolic pathway.
21
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Functions of Membrane Proteins CELL MEMB.

3-Signal transduction:
 A membrane Lipid-anchored protein may have a binding
site with a specific shape that fits the shape of a chemical
messenger, such as a hormone. The external messenger
(signal) may cause a conformational change in the protein
(receptor) that relays the message to the inside of the
cell.
 They include the G proteins, which are named for their
ability to bind to guanosine triphosphate (GTP) and
participate in cell signaling in response to certain
hormones.
4- Cell-cell recognition:
 Some glycoproteins serve as identification tags that are

22 specifically recognized by other cells.

Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Functions of Membrane Proteins CELL MEMB.

5- Intercellular joining:
 Membrane proteins of adjacent cells may hook
together in various kinds of junctions, such as gap
junctions or tight junctions.
6- Attachment to the cytoskeleton and
extracellular Matrix (ECM):
 Microfilaments or other elements of the cytoskeleton
may be bonded to peripheral membrane proteins, a
function that helps maintain cell shape and stabilizes
the location of certain membrane proteins.
 Proteins that adhere to the ECM can coordinate
extracellular and intracellular changes.
23
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Carbohydrates & Cell-Cell Recognition CELL MEMB.

 They are usually branched oligosaccharides.

 Some are covalently bonded to lipids (glycolipids), most are covalently

bonded to proteins (glycoproteins).
 Vary from species to species, between individuals of the same species and
among cells in the same individual.
Cell-Cell Recognition:
 Cell-cell recognition is the ability of a cell to determine if other cells it

encounters are alike or different from itself.

 Cell-cell recognition is crucial in the functioning of an organism as it is the

basis for sorting of an animal embryo's cells into tissues and organs and the
rejection of foreign cells by the immune system.
24
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membrane Carbohydrates & Cell-Cell Recognition CELL MEMB.

Cell-Cell Recognition:
 The way cells recognize other cells is probably by keying on cell markers
found on the external surface of the cell membrane. Because of their
diversity and location, membrane carbohydrates are good candidates.
 The blood grouping A, B, AB and O are based on oligosaccharides found
on the RBC’s membrane.

25
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
The Membrane Fluidity CELL MEMB.

 Membranes are held together by hydrophobic interactions.

 Most membrane lipids and some proteins can drift laterally within the
membrane.
 Molecules rarely flip transversely across the membrane, because
hydrophilic parts would have to cross the membrane's hydrophobic core.
Lipid Movements:
• Phospholipids can drift laterally in the plane of
the membrane (an average lipid molecule can
diffuse the length of a large bacterial cells (~ 2 μm)
in about 1 second) = lateral movement (frequently)
• Also, phospholipids can migrate from the
monolayer on one side to that on the other = flip-
flop (rarely).
26
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
The Membrane Fluidity CELL MEMB.

Lipid Movements:
 Temperature and lipid composition determine fluidity of the membrane.
 -At low temperature, membrane is less fluid and because the phospholipids
are more closely packed.
• Membranes rich in unsaturated fatty
acids are;
more fluid that those dominated by
saturated.
fatty acids because the kinks in the
unsaturated.
fatty acid tails prevent tight
packing.
27
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
The Membrane Fluidity CELL MEMB.

Lipid Movements:
 Steroid cholesterol which is wedged
between phospholipids also effects
membrane fluidity.
 At warm temperature, it makes membrane
less fluid by restraining the movement of
phospholipid.
 At low temperature, the membrane
remains fluid because cholesterol hinders
the close packing of the phospholipids.
 Membrane proteins drift more slowly than
lipids
28
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membranes are Asymmetrical CELL MEMB.

 Carbohydrates are found only on the outer side of the bilayer.

 Glycolipids are differentially arranged as well and are always on the

outer leaflet with their attached carbohydrate projecting away from

the cell.
 Glycoproteins are similarly oriented on the outer leaflet with
carbohydrates projecting into the environment.
 Peripheral membrane proteins are attached only to the inner membrane

leaflet, facing the cytoplasm. Therefore, the inner and outer

membrane leaflets have different compositions and each can have
functions distinct from those of the other.
29
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membranes are Asymmetrical CELL MEMB.

 Cholesterol can readily flip-flop or move from one leaflet to the other and is
distributed on both sides of the membrane bilayer.
 The different types of phospholipids are distributed asymmetrically in the 2
phospholipid layers: PC is usually in the outer layer and PS, PI and PE are in
the inner bilayer.
 The asymmetry is maintained by a "lipid pump" which requires ATP

energy.

 Purpose of the asymmetry is unknown but may have something to do

with membrane fusion and bending.

 The inner surface is supported by the cytoskeleton; some peripheral

30
membrane proteins attach to the cytoskeleton.
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Membranes are Asymmetrical CELL MEMB.

 During the process of programmed cell death, phosphatidylserine is

transferred enzymatically from the inner leaflet to the outer leaflet of the
membrane. The presence of phosphatidylserine on the outer leaflet then
triggers phagocytic removal of the dying cells, emphasizing further that the
maintenance of membrane asymmetry is important for normal cell function.

31
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
New membrane synthesis CELL MEMB.

 Synthesis of molecules starts in the

inside face or the endoplasmic
reticulum (ER) and ends up on the
outside face of the plasma
membrane.
 Synthesis of membrane proteins and
lipids in ER (making glycoproteins
after modification).
 Inside Golgi apparatus, carbohydrates
gets further modification and lipids
become glycolipids.
32
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
New membrane synthesis CELL MEMB.

 Transport proteins, secretory

proteins and glycolipids are

transported in vesicles to the
plasma membrane.
 Vesicle fuses with the
membrane releasing secretory
proteins from the cell and
depositing glycoproteins and
glycolipids on the surface of the
cell.
33
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
Reference CELL MEMB.

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=mcb.TOC

mohamed.kotb71524@gmail.com
WhatsApp: 00201140400767
https://www.facebook.com/drmohamed.k.elsayed
https://www.researchgate.net/profile/Mohamed_kotb_Kotb-El-Sayed2

34
Dr. Mohamed I. Kotb – Associate Professor of Pharmaceutical Biochemistry and Molecular Biology
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