Chapter 5:

General Structure of Cell Membrane:

Major structural components of the Cell Membrane:

1. Phospholipid bilayer
2. Transmembrane proteins:
An integral membrane protein that spans the entirety of the cell membrane,
inclusive of Carrier, Channel and Receptor proteins.
3. Interior protein network:
A protein either spectrin or clathrin links integral membrane proteins with actin
filaments in the cell’s cytoskeleton.
4. Cell surface markers:
Can exist as glycoprotein, or glycolipid on the outer surface of the plasma membrane
that identify the cell type. These markers are assembled in the ER, transferred to the
Golgi apparatus before being transferred to the plasma membrane.
5. NOT extracellular matrix

General structure of cell membrane:

Integral proteins protrude through the plasma membrane, with nonpolar regions that tether
them to the membrane’s hydrophobic interior. Carbohydrate chains are often bound to the
extracellular portion of these proteins, forming glycoproteins. Peripheral membrane
proteins are associated with the surface of the membrane. Membrane phospholipids can be
modified by the addition of carbohydrates to form glycolipids. Inside the cell, actin filaments
and intermediate filaments interact with membrane proteins. Outside the cell, many animal
cells have an elaborate extracellular matrix composed primarily of glycoproteins.
 The phospholipid bilayer
 The phospholipid bilayer is the basic structure of every plasma membrane
 Made up of 2 layers of phospholipids with the nonpolar end facing each other in the
interior, while the polar hydrophilic head facing the exterior
 The non-polar tails of phospholipid molecules are made up of fatty acids molecules.
They face each other in the interior of the plasma membrane and form a hydrophobic
barrier to polar molecules
 The polar head of phospholipid molecules, contains a phosphate group and face the
exterior of the plasma membrane. The polar heads are hydrophilic and able to interact
with water molecules.
 This allows the phospholipid molecules to form a bilayer spontaneously, driven by the
tendency of water molecules to form the maximum number of hydrogen bonds.**
 Because phospholipids interact relatively weakly with one another, individual
phospholipids and unanchored proteins are comparatively free to move about within
the membrane. The membrane is said to be fluid.
 Animal cell membranes also contain a significant amount of cholesterol, a steroid with
polar hydroxyl group. Plant cells have other sterols, but little to no cholesterol.
 The phosphate in a phospholipid molecule can also be modified with polar organic
molecules.
 Ions interact well with polar molecules but are repelled by the hydrophobic interior of
the lipid bilayer.

**Hydrogen bonds:  It is important to be clear that although it is called "hydrogen-bonding"

it really is an intermolecular force. It is also vital that you refer to the hydrogen bonding as
being between molecules and not within them. It exists where one of the most
electronegative elements (fluorine, oxygen or nitrogen) is bonded to hydrogen. The water
molecules tend to form the maximum hydrogen bonds to obtain stability. Thus the water
molecules will form hydrogen bonds with the phospholipid bilayer, causing the phospholipid
bilayer to form.
Phospholipid (Revision)
Structurally consists of:

1. Glycerol: a 3-carbon polyalcohol

2. Two fatty acids: attached to the glycerol, nonpolar and hydrophobic (“water-
fearing”)
3. Phosphate group: attached to the glycerol, polar and hydrophilic (“water-loving”)

The phospholipid molecule can be thought of as having a polar “head” at one end (the
phosphate group) and two long, very nonpolar “tails” at the other. Molecules with both
polar and nonpolar regions are called amphipathic.

The Fluid Mosaic Model of Cell Membrane

 Since the cell membrane is made up of a mixture of lipids (phospholipids, cholesterol),
carbohydrates and proteins → Mosaic
 Phospholipids interacts relatively weakly with one another; individual phospholipids and
unanchored proteins are comparatively free to move about within the membrane →
Fluid
 Fluidity is defined as the “ability of molecules to readily move throughout the
membrane while staying in close association with other molecules”.
 As the temperature is increased, the membrane becomes more fluid.
 As the temperature increases the kinetic energy of the phospholipid molecules
increases. As a result, the weak intermolecular bonds are broken and the structure
collapses, becoming less ordered and more fluid.
 The degree of fluidity can be altered by changing the fatty acid composition – increase
unsaturated fatty acids make the membrane more fluid
 When there are unsaturated fatty acids that have a cis double bond that forms a kink
which prevents the phospholipid molecules to be easily packed, as there is lesser
interaction between the molecules.
 Increase in cholesterol in the plasma membrane can increase the strength of plasma
membrane but also decrease membrane fluidity (normal temperatures)
 In animals cells, cholesterol may make up as much as 50% of membrane lipids in the
outer leaflet.
 Cholesterol helps to maintain fluidity in the plasma membrane. Membranes with high
amounts of cholesterol are very stable and have decreased permeability.
 Membrane fluidity is thus affected by temperature, cholesterol, types of fatty acids

Membrane Proteins: Types and Functions

 Membrane proteins are a collection of proteins that float in the lipid bilayer
 Many of the proteins are not fixed in position but can move around like the phospholipid
molecules
 Two types:
1. Integral membrane proteins: Proteins that are embedded within the membrane
2. Peripheral membrane proteins: Proteins that are associated with the surface of
the membrane

Function of membrane proteins

1. Cell to cell adhesion proteins e.g., Tight Junctions, cadherin

2. Enzymes which carry out chemical reactions on the interior of the plasma membrane
e.g., electron transport chains (found) in mitochondria and chloroplasts
3. Transporters e.g., ion channels of the plasma membrane
4. Cell surface Receptors they detect chemical messages. e.g., Receptor Tyrosine Kinase
(RTK), G-Protein Coupled Receptor (GPCR), green protein are substances such as
hormones.
5. Cytoskeleton Anchors, proteins attach to both microfilaments or intermediate
filaments, but usually not microtubules.
6. Cell surface identity Markers e.g., glycoproteins, Cluster of Differentiation (CD), allows
the WBC to identify. Glycolipids can also be cell surface markers
Acronym: JET RAM
 Channel proteins allow straight diffusion, while for carrier proteins the molecules must
bind with the protein first
 Glucose and sucrose can pass with help.
 NH3 is a polar molecule which diffuses across a phospholipid bilayer faster than water.
 Water is a polar molecule that diffuses very slowly through the lipid bilayer
 However, water diffuses rapidly through channel membrane proteins called aquaporins.

Transmembrane Proteins
 A type of integral membrane proteins that span the entirety of cell membrane
 Typically made up of 3 domains
1. Extracellular domain
2. Transmembrane domain
3. Intracellular (cytoplasmic) domain
 Transmembrane domains are in contact with the nonpolar interior of the membrane and
consisted primarily of nonpolar amino acids.
 The extracellular and cytoplasmic domains tend to have more charged and polar amino
acids
 The polar water molecules exclude nonpolar amino acids (hydrophobic exclusion),
keeping transmembrane domains within the interior of the lipid bilayer.
 Transmembrane domains are composed of nonpolar amino acids and often form a
helices.
 Transmembrane proteins
Transmembrane domains: Integral membrane proteins have at least one hydrophobic
transmembrane domain (shown in blue) to anchor them in the membrane. a. Protein with a
single transmembrane domain e.g. cadherin. b. Receptor protein with seven
transmembrane domains e.g. GPCR

Movement of Substances Across Cell Membrane

There are 3 basic mechanisms by which substances move across cell membrane
1. Passive transport
2. Active transport
3. Bulk transport

Mechanism Example
Passive transport  Diffusion
 Facilitated diffusion:
1. Ion channels
2. Carrier protein
 Osmosis (water)
 Down a concentration gradient
 Does not need energy
Active transport  Sodium- Potassium (Na+-K+) Pump
 Coupled transport
 Against a concentration gradient
 Requires energy
Bulk transport  Endocytosis
1. Phagocytosis
2. Pinocytosis
3. Receptor mediated endocytosis
 Exocytosis
What is Passive transport
 Passive transport is the movement of molecules down a concentration gradient without
the need for energy.
 For example:
1. Simple diffusion
2. Facilitated diffusion
3. Osmosis

Simple Diffusion and Facilitated Diffusion

Simple Diffusion
 Movement of molecules from high concentration to low concentration
 No energy is required
 Will continue until the concentration is the same in all regions
 Diffusion is caused by random movement of all atoms and molecules.
 As the solute concentration increases, the rate of diffusion increases but eventually it
remains constant once it reaches a maximum rate.
 E.g. movement of oxygen and non-polar molecules such as steroid hormones which can
freely cross the cell membrane
Example:
Diffusion: (a) If a drop of colored ink is dropped into a beaker of water, its molecules
dissolve (b) and diffuse (c) Eventually diffusion results in an even distribution of ink
molecules throughout the water (d).

Facilitated Diffusion
 Polar molecules or ions cannot diffuse across the phospholipid bilayer of plasma
membrane and requires facilitated diffusion
 Like simple diffusion, requires no energy and substances move down a concentration
gradient.
 As the solute concentration increases, the rate of diffusion increases but eventually it
remains constant once it reaches a maximum rate.
 Two mechanisms of facilitated diffusion
1. Through ion channels (no binding)
2. Through carrier proteins (binding)
 Carrier-mediated transport is also called facilitated diffusion
 In RBC facilitated diffusion, chloride ions are transported in one direction and
bicarbonate ions in the opposite direction.
 For glucose transport in RBC, to prevent glucose from leaving passively, it is
phosphorylated so it can no longer bind to the glucose transporter and leave the cell.
 Only facilitated diffusion by carrier proteins reaches a saturation point where all carrier
proteins are occupied and the rate of transport cannot increase.
** Facilitated diffusion is where membrane proteins are involved when no membrane
proteins are involved.
Ion Channels
 Possess a hydrated interior that spans the membrane
 Ions can diffuse through the channel in either direction, depending on their relative
concentration across the membrane
 Some channel proteins can be opened or closed in response to a stimulus, either
chemical or electrical. This is known as gated channels, requires a signal molecule or a
specific chemical (also called a ligand) which binds to it.
 Each type of channel is specific for a particular ion, such as calcium (Ca2+), sodium (Na+),
potassium (K+), or chloride (Cl-), or in some cases, for more than one cation or anion

Facilitated diffusion through ion channels

Diffusion can be facilitated by membrane proteins. a. The movement of ions through a
channel is shown. On the left the conc gradient is higher outside the cell, so the ions move
into the cell. On the right the situation is reversed. In both cases, transport continues until
the concentration is equal on both sides of the membrane. At this point, ions continue to
cross the membrane in both direction, but there is no net movement in either direction.
Carrier Proteins
 Can transport ions and other solutes such as sugars, amino acids
 Requires a concentration gradient difference across the membrane before diffusion
happens
 Rate of transport limited by the number of transporters, can become saturated.

Facilitated diffusion by carrier protein

Carrier proteins bind specifically to the molecules they transport. In this case the
concentration is higher outside the cell, so molecules bind to the carrier on the outside. The
carrier’s shape changes, allowing the molecule to cross the membrane. This is reversible, so
the net movement continues until the concentration is equal on both sides of the
membrane.
 Ion Channels Carrier Proteins
Energy required No No
Up/down concentration Moves DOWN a Moves DOWN a
gradient concentration gradient concentration gradient
Direction of movement Ions can be transported in Molecules can be
either direction transported in either
direction
Mechanism Ions diffuse through the Molecules bind with carrier
hydrated interior of the protein and are then
channel protein that spans transported across the
the membrane membrane by a subsequent
change in the shape of
carrier protein
Control of movement Some channel proteins Rate of transport limited by
(gated channels) can be number of transporters, can
opened or closed in become saturated.
response to a stimulus,
either chemical or electrical
Specificity Each type of channel is Each carrier proteins is
specific for a particular ion, specific to the kind of
such as calcium, sodium, molecule it binds to (can
potassium, or chloride, or in transports), in some cases,
some cases, for >1 kind of for >1 kind of molecule E.g.
cation or anion sodium-potassium pump.
Types of molecules Ions Ions and other solutes such
as sugars, amino acids
Structure Has a hydrophilic interior Has a hydrophilic interior
channel channel
Osmosis

 Definition: The net movement of water molecules across a partially permeable

membrane from a region of a lower solute concentration (Higher WP) to a region of
higher solute concentration (lower WP).
 For cells: Osmosis is the net movement of water molecules across the partially
permeable membrane of the cell or the aquaporins from a region of higher water
potential to a lower water potential.
 Water molecules interact with dissolved solutes by forming hydration shells around the
charged or polar solute molecules. (Whereby water molecules gather around each polar
or charged molecule. )
 High concentration of solute result in less free water molecules
 Low concentration of solute will have more free water molecules
 Free water molecules move down their concentration gradient, towards the higher
solute concentration
 Water molecules moves across the membrane by osmosis through water protein
channels known as aquaporins (channel proteins)
 Osmotic concentration tells the amount of solutes in the solution (high for more solutes,
vice versa)
 Can use water potential too.

Osmosis:
 Concentration differences in charged or polar molecules that cannot cross selectively
permeable membrane result in the movement of water molecules, which can cross the
membrane.
 Water molecules form hydrogen bonds with urea molecules, creating a hydration shell
around them in solution whereby water molecules gather around urea molecule.
 These water molecules are no longer free to diffuse across the membrane.
 The polar solute has reduced the concentration of free water molecules, creating a
gradient.
 This causes a net movement of water by diffusion from right to left in the U-tube, raising
the level on the left and lowering it on the right.

Osmotic Concentration
The concentration of all solutes in a solution determines the osmotic concentration of the
solution. The higher the concentration of solutes, the higher the osmotic concentration
(lower
water potential)

Osmotic concentration is directly proportional to the solute concentration

 Solution with higher osmotic concentration is said to be hypertonic (lower WP)
 Solution with lower osmotic concentration is said to be hypotonic (higher WP)
 Solution with the same osmotic concentration is said to be isotonic

How solutes create osmotic pressure: 

In a hypertonic solution, water moves out of the cell.
In an isotonic solution, water diffuses into and out of the cell at the same rate.
In a hypotonic solution, water moves into the cell.
Water enters the cell due to osmotic pressure from the higher solute concentration in the
cell. (Osmotic pressure is also the pressure the causes osmosis, because of Newton’s third
law, every action has an equal an opposite reaction)
Osmotic pressure is measured as the force needed to stop osmosis.

Type of cells Effect in concentrated Effect in dilute solution

solution
Plant cell  Plasmolysis occurs  Hydrostatic pressure
when cells are placed in results in when cells are
concentrated solution. placed in a dilute
 Water leaves the cells solution.
 Vacuole decreases in  Water enters the cell
size  Vacuole increase in size
 Cytoplasm shrinks away  Cellulose cell wall
from the cell wall. prevents over expansion
of the cell membrane by
exerting an opposing
pressure.
 When cell is fully turgid
further entry of water is
prevented

Red blood cell  Crenation occurs when  Haemolysis occurs when

cells are placed in a cells are placed in a
hypertonic solution hypotonic solution.
 Water leaves the cell  Water molecules enters
 Membrane of the cell the cell
forms little spikes  Animal cells do not have
 Cell shrinks, becomes walls to prevent over
dehydrated and dies expansion of the cell
membrane to withstand
the hydrostatic pressure
 The cell expands and
lyse
What is Active Transport

 Movement of substances across the plasma against the concentration gradient through
a ppm
 Requires the expenditure of energy in the form of ATP
 Involves highly selective protein carriers within the membrane that bind to the
transported substances e.g. ions, sugar, amino acid, or nucleotide
 Uniporters: transport a single type of molecule
 Symporters: transport 2 types of molecules in the same direction
 Antiporters: transport 2 types of molecules in opposite direction e.g. Sodium-
Potassium pump

Sodium-Potassium Pump (Antiporters)

 Most animal cells have a low concentration of Na+, relative to their surroundings, and a
high internal concentration of K+
 Cells maintain these concentration differences by actively pumping Na + out of the cell
and pumping K+ in
 Sodium-potassium pump is an antiporter carrier protein
 Use the energy stored in ATP (Adenosine triphosphate) to power the simultaneous
movement of these two ions
 Also uses energy from ATP to alter the conformation of the carrier protein
 By changing the conformation of the carrier protein, which in turn changes its affinity
first for Na+ ions and then for K+ ions
 The sodium-potassium pump transports sodium and potassium across the plasma
membrane. Every 3 sodium transported out of the cell, 2 potassium are transported in.
The Sodium or potassium is fuelled by ATP hydrolysis. The affinity of the pump for
sodium and potassium is changed by addition/ removal of Phosphate (P), which changes
the conformation of the protein.
Three Na+ bind to the cytoplasmic side of the protein, causing the protein to change its
Conformation (initiates the sodium-potassium pump)

In its new conformation, the protein binds a molecule of ATP and cleaves it into adenosine
diphosphate (ADP) and phosphate (Pi). ADP is released, but the phosphate group is
covalently linked to the protein. The protein is said to be phosphorylated.
The phosphorylation of the protein induces a second conformational change in the protein.
This change translocates the three Na+ across the membrane, so they now face the
exterior. In this new confirmation, the protein has a low affinity for Na +, and the three
bound Na+ break away from the protein and diffuse into the extracellular fluid

The new conformation has a high affinity for K+, two of which bind to the extracellular side
of the protein as soon as it is free of the Na+

The binding of the K+ causes another conformational change in the protein, this time
resulting in the hydrolysis of the bound phosphate group.
Freed of the phosphate group, the protein reverts to its original shape, exposing the two K +
to the cytoplasm. This conformation has a low affinity for K+, so the two bound K+ dissociate
form the protein and diffuse into the interior of the cell, The original conformation has a
high affinity for Na+. When these ions bind, they initiate another cycle.
Coupled Transport by Symporters and Antiporters
 During coupled transport, carrier proteins create a concentration gradient using energy
from ATP. When the ions or molecules diffuse back down their concentration gradient,
energy is released and used to move another substance against its own concentration
gradient, thus using energy stored in ATP indirectly. (secondary active transport)
 For example: active transport of glucose (carried out by symporter)
 The glucose symporter uses the Na+ gradient produced by the sodium-potassium pump
as a source of energy to power the movement of glucose into the cell
 Both glucose and Na+ simultaneously bind to the symporter transport system
 Glucose moves against the concentration gradient
 Na+ passes into the cell down its concentration gradient caused by using energy from
ATP to create the concentration gradient, carrying glucose along with it into the cell.

1) The energetically-favourable movement of Na+ down its electro chemical gradient is

coupled to
2) Transport of glucose
Coupled transport with a symporter

Coupled transport (example of a symporter): A membrane protein transports Na+ into the

cell down a concentration gradient maintained by the Na+/K+ pump, at the same time
transporting a glucose molecule. The concentration gradient driving the Na + entry allows
sugar molecules to be transported against their concentration gradient.

Endocytosis & Exocytosis

The lipid nature of a cell’s plasma membranes creates an interesting problem for the cell.
The substances that cells require for growth are mostly large polar molecules that cannot
cross the hydrophobic barrier a lipid bilayer creates. Two processes are involved in this bulk
transport: endocytosis and exocytosis.

Endocytosis

 Movement of substances into the cell

 Requires energy
 The plasma membrane envelopes food particles and fluids in 3 ways:
1. Phagocytosis
2. Pinocytosis
3. Receptor-mediated endocytosis

Phagocytosis
When taking in particulate matter (eat) (discrete particles)
In phagocytosis, the cell membrane surrounds the particle and engulfs it
Pinocytosis
When taking in fluid (drink)
In pinocytosis, the cell membrane invaginates, surrounds a small volume of fluid which
pinches off.
Receptor-mediated phagocytosis
For specific molecule
In receptor-mediated endocytosis, uptake of substances by the cell is targeted to a single
type of substance (E.g. LDL) that binds to receptors on the external surface of the cell
membrane.

Phagocytosis of a bacterium

Pinocytosis of a smooth muscle cell

Receptor Mediated Endocytosis

 Cells have pits coated with the protein clathrin

 Endocytosis is initiated when the target molecule binds to receptor proteins in the
plasma membrane
 The pit will deepen and eventually seal off to form a vesicle
 For example: Intake of cholesterol in the cell by LDL (low density lipoprotein) receptor

In receptor-mediated endocytosis, cells have pits coated with the protein clathrin that
Initiate endocytosis when target molecules bind to receptor proteins in the plasma
Membrane. When an appropriate collection of molecules gathers in the coated pit, the pit
deepens and will eventually seal off to form a vesicle

Exocytosis
 Movement of substances out of the cell
 Requires energy
 Proteins and other molecules are secreted from cells in small vesicles
 Vesicle membranes fuse with the plasma membrane, releasing their contents outside
the cell
 For example: Secretion of hormones, digestive enzymes in animal cell.

Excretion Secretion
Waste products Hormones
Enzymes
Antibodies
Signalling molecules

Exocytosis is also a mechanism by which cells are able to insert membrane proteins, cell
surface receptors, lipids and other components into the cell membrane.
Vesicles containing these membrane components fully fuse with an become part of the cell
membrane.
Excretion: wastes going out
Secretion: useful substances going out