Cell and Molecular
Biology
Ninth Edition

Gerald Karp, Janet Iwasa, Wallace Marshall

Chapter 4
The Structure and Function of the Plasma
Membrane

4.0 | Nerve Gas
 Sarin is a type of nerve gas—a chemical weapon that
interferes with the nervous system.
 This chapter will demonstrate how proteins in the cell
membrane convert chemical signals to electrical signals
that are required for many physiological activities.

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4.1 | Introduction to the Plasma Membrane
(1 of 3)
 Plasma membrane: The outer boundary of the cell that separates it from
the world is a thin, fragile structure about 5–10 nm thick.
 Need electron microscope to examine.
 All membranes examined closely from plants, animals or microorganisms
have the same ultrastructure.

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4.1 | Introduction to the Plasma Membrane
(2 of 3)
An Overview of Some of Membrane Functions
 Transporting solutes
 Responding to external signals
 Intracellular interaction
 Selectively permeable barrier
 Energy transduction

A summary of membrane functions in a
plant cell
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4.1 | Introduction to the Plasma Membrane
(3 of 3)
A Brief History of Studies on Plasma Membrane Structure
 Membranes were found to be
mostly composed of oil.
 The lipid bilayer accounted for
the 2:1 ratio of lipid to cell
surface area.

Calculating the surface area of a lipid
preparation
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4.2 | The Chemical Composition of Membranes
(1 of 6)
 Membranes are made of lipid–
protein assembly
 The ratio of lipid to protein varies
 The myelin sheath acts as
electrical insulation for the nerve
cell

Electron micrograph of a nerve cell axon
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4.2 | The Chemical Composition of Membranes
(2 of 6)
Membrane Lipids
 Membrane lipids are amphipathic which contain both hydrophilic and
hydrophobic regions.
 Phosphoglycerides, sphingolipids and cholesterol are types of this.

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4.2 | The Chemical Composition of Membranes
(3 of 6)
Membrane Lipids: Phosphoglycerides
 Lipids with a phosphate group
are phospholipids.
 Phospholipids built on a glycerol
backbone are called
phosphoglycerides.
 Fatty acyl chains are hydrophobic
 A fatty acid may be fully
saturated, monounsaturated, or
polyunsaturated.

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4.2 | The Chemical Composition of Membranes
(4 of 6)
Membrane Lipids: Cholesterol
 Cholesterol is smaller and less
amphipathic.
 A sterol that makes up to 50% of
animal membrane lipids.
 Carbon rings are flat and rigid.

Cholesterol molecules (green) oriented
with their small hydrophilic end facing the
external surface of the bilayer
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4.2 | The Chemical Composition of Membranes
(5 of 6)
The Nature and Importance of the Lipid Bilayer
 Membranes form extensive
inter-connected networks
within the cell.
 Lipid bilayers are flexible.

Movement: ruffling of
the plasma membrane
of a migrating cell

 The lipid bilayer helps to
maintain the proper
internal composition of a
cell.

Division: invagination of
the plasma membrane
during cell division

Fusion: plasma membranes
of sperm and egg unite

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4.2 | The Chemical Composition of Membranes
(6 of 6)
The Nature and Importance of the Lipid Bilayer
 The lipid bilayer can selfassemble
 Liposomes have proven
invaluable in membrane
research.
 Membrane proteins can be
inserted into liposomes.
 Liposomes are vehicles to deliver
drugs or DNA within the body
Liposomes: synthetic vesicles
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4.2 | Membrane Carbohydrates (1 of 2)
 Plasma membranes of eukaryotic
cells have carbohydrate,
glycoproteins and glycolipids.
 Oligosaccharides may be attached
to several different amino acids by
two types of linkages: N-linkages
and O-linkages.
 Carbohydrate projections play an
important role in mediating the
interactions of a cell with its
environment.

Two types of linkages that join sugars to a
polypeptide chain
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4.2 | Membrane Carbohydrates (2 of 2)
 Glycolipid carbohydrates of the red
blood cell plasma membrane
determine whether a person's
blood type (A, B, AB, or O).
 A: Enzyme adds Nacetylgalactosamine to the end of
the chain.
 B: Enzyme adds galactose to the
chain terminus.
 AB: Both enzymes present.
 O: Lack enzymes capable of
attaching either terminal sugar.
Blood-group antigens
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4.3 | Membrane Proteins (1 of 2)
Integral Membrane Proteins
 Integral membrane proteins
function as receptors that bind
ligands, channels or transporters
to move ions/solutes across the
membrane.
 They are amphipathic, having
both hydrophilic and
hydrophobic portions.
 This preserves the permeability
barrier of the membrane.
Driven by van der Waals forces between
amino acids and lipids, proteins can be
surrounded by a closely applied shell of
lipid molecules.
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4.3 | Membrane Proteins (2 of 2)
Peripheral Membrane Proteins
 Peripheral proteins associate with the membrane by weak
electrostatic bonds.
 Other cytosolic peripheral proteins act as enzymes,
specialized coats, or factors that transmit transmembrane
signals.
 Peripheral proteins typically have a dynamic relationship with
the membrane, being recruited or released as needed.

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4.3 | Studying the Structure and Properties of
Integral Membrane Proteins
 It is very difficult to obtain
crystals of integral membrane
proteins for X-ray crystallography
 Most solved structures are
prokaryotic versions that are
smaller than eukaryotic versions.
 Homology modeling is used to
learn about the structure and
activity of members of a protein
family.

An integral protein as it resides within the
plasma membrane

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4.4 | Membrane Lipids and Membrane Fluidity
(1 of 3)
 Physical state of the membrane lipid is described by its fluidity or
viscosity.
 If the temperature of the bilayer is kept relatively warm (37˚C), the lipid
exists in a relatively fluid state.
 Molecules retain a specified orientation.

Structure of the lipid bilayer depends on the temperature: above and below the transition
temperature
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4.4 | Membrane Lipids and Membrane Fluidity
(2 of 3)
Maintaining Membrane Fluidity
 Internal temperatures of most organisms can fluctuate with the
temperature, so cells respond by altering phospholipid composition.
 Desaturation is catalyzed by desaturases.
 The cell changes the types of phospholipids being synthesized in favor of
ones containing more unsaturated fatty acids.

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4.4 | Membrane Lipids and Membrane Fluidity
(3 of 3)
Lipid Rafts
 The outer leaflet of plasma membrane contains specialized regions.
 Cholesterol and sphingolipids tend to pack together to form highly
ordered microdomains forming lipids rafts.
 They provide a favorable environment for cell-surface receptors.

(left) Sphingomyelin organizing
into orange-colored rafts; (right)
Schematic model of a lipid raft

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4.5 | The Dynamic Nature of the Plasma
Membrane (1 of 7)
 A phospholipid can move
laterally.
 A phospholipid can diffuse from
one end of a bacterium to the
other end in a second or two.
 Flippases are enzymes that move
certain phospholipids from one
leaflet to the other.

The possible movements of phospholipids
in a membrane
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4.5 | The Dynamic Nature of the Plasma
Membrane (2 of 7)
The Diffusion of Membrane Proteins after Cell Fusion
 Cell fusion is a technique whereby two different types of cells, or cells
from two different species, can be fused to produce one cell.
 Labeled proteins have shown that membrane proteins can move
between fused cell.

Cell fusion to reveal mobility of membrane proteins: fusion of human and mouse cells
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4.5 | The Dynamic Nature of the Plasma
Membrane (3 of 7)
The Diffusion of Membrane Proteins after Cell Fusion
 Proteins can be labeled
and tracked.
 Proteins can be immobile,
mobile in a directed
manner, or exhibit
random movement.

Measuring the diffusion rates of membrane proteins by
FRAP: variable nature of fluorescence recovery is dependent
upon the protein examined
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4.5 | The Dynamic Nature of the Plasma
Membrane (4 of 7)
Control of Membrane Protein Mobility
 Protein movements are slower
than predicted by protein size
and membrane viscosity.
 Protein movements are limited
by various interactions.
 Some proteins have barriers to
lateral diffusion.

Patterns of movement of integral
membrane proteins
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4.5 | The Dynamic Nature of the Plasma
Membrane (5 of 7)
Membrane Lipid Mobility
 Phospholipid diffusion is
restricted within the bilayer.
 Phospholipids are confined for
very brief periods to certain
areas.
 Fences restricting motion are
constructed of rows of integral
membrane proteins.
Experimental demonstration that diffusion
of phospholipids within the plasma
membrane is confined
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4.5 | The Dynamic Nature of the Plasma
Membrane (6 of 7)
Membrane Domains and Polarity
 Most membranes vary in
protein composition and
mobility.
 The epithelial cells that line the
intestines and kidneys have
highly polarized cells.
 The apical plasma membrane
absorbs substances from the
lumen.
Differentiated functions of the plasma
membrane of an epithelial cell
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4.5 | The Dynamic Nature of the Plasma
Membrane (7 of 7)
Membrane Domains and Polarity
 Sperm may have the most highly
differentiated structure.
 A sperm is covered by a
continuous plasma membrane.
 Antibodies can detect and reflect
the distribution of different
proteins.

Differentiation of the mammalian sperm
plasma membrane as revealed by fluorescent
antibodies
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4.5 | The Red Blood Cell: An Example of Plasma
Membrane Structure (1 of 2)
 The plasma membrane of the
human erythrocyte is the most
studied and best understood.
 Membrane proteins can be purified.

SEM of human erythrocytes and
membrane ghosts
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4.5 | The Red Blood Cell: An Example of Plasma
Membrane Structure (2 of 2)
The Erythrocyte Membrane Skeleton
 The major component of
the internal membrane
skeleton is spectrin.
 Spectrin molecules are
attached to the membrane
surface to ankyrin.
 Spectrin is linked to other
cytoplasmic proteins as
well.

EM: inner membrane skeleton proteins
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4.6 | Movement Of Substances Across Cell
Membranes
 Selective permeability allows for
separation and exchange of
materials across the plasma
membrane
 Net flux is the difference
between influx and efflux of
materials.
 Substances move across
membranes by diffusion and
active transport.

Four basic mechanisms by which solute
molecules move across membranes
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4.6 | Diffusion Through the Lipid Bilayer (1 of 2)
The Diffusion of Water Through Membranes
 Diffusion of water through a semipermeable membrane is called
osmosis.
 Cells swell in hypotonic solution, shrink in hypertonic solutions, and
remain unchanged in isotonic solutions.

The effects of differences in the concentration of solutes on opposite sides of the plasma
membrane
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4.6 | Diffusion Through the Lipid Bilayer (2 of 2)
The Diffusion of Water Through Membranes
 Plants utilize osmosis in different
ways as they are usually
hypertonic compared to their
fluid environment.
 There is a tendency for water to
enter the cell.
 In hypertonic solutions the plant
cell undergoes plasmolysis.

The effects of osmosis on a plant cell
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4.6 | The Diffusion of Ions through Membranes
(1 of 2)
Most ion channels can exist in either an open or a closed
conformation, and are called gated. The three major
categories of gated channels are:
1. Voltage‐gated channels: Conformational state depends
on the difference in ionic charge on the two sides of
the membrane.
2. Ligand‐gated channels: Conformational state depends
on the binding of a specific molecule (ligand).
3. Mechano‐gated channels: Conformational state
depends on mechanical forces that are applied to the
membrane.
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4.6 | The Diffusion of Ions through Membranes
(2 of 2)
 Once opened, more than 10
million K+ ions can pass through
per second.
 After the channel is open for a
few milliseconds, the movement
of K+ ions is “automatically”
stopped.
 Can exist in three different states:
open, inactivated, and closed.

Conformational states of a voltage-gated K+
ion channel
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4.6 | Experimental Pathways (1 of 2)
The Acetylcholine Receptor
 Researchers have focused on
determining the structure of the
nAChR.
 Site‐directed mutagenesis has
helped determine the residues
that span the membrane.
 Electron micrographs showed the
receptors as ring shaped.

Electron micrograph characterization of
the nAChR

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4.6 | Experimental Pathways (2 of 2)
The Acetylcholine Receptor
 Unwin used electron crystallography to analyze the structure of the
nAChR.
 The ion channel consists of a pore lined by a wall of five inner (M2) a
helices, one from each surrounding subunit.
 The gate opens following the binding of two ACh molecules, one per a
subunit.

Electron density map of a slice
through the nAChR and schematic
diagram showing the subunit
arrangement
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4.6 | Facilitated Diffusion (1 of 2)
 In many cases, the diffusing
substance binds selectively to a
membrane-spanning protein,
called a facilitative transporter.
 Facilitated transporters can
mediate the movement of
solutes in both directions.
 Facilitated diffusion is similar to
an enzyme-catalyzed reaction.

Schematic model of facilitated diffusion

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4.6 | Facilitated Diffusion (2 of 2)
 Insulin plays a key role in
maintaining proper blood sugar
levels.
 An increase in blood glucose
levels triggers the secretion of
insulin, which stimulates the
uptake of glucose.
 Rising insulin levels stimulates
the movement of transporters
to the cell surface.
Kinetics of facilitated diffusion compared
to simple diffusion

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4.6 | Active Transport (1 of 5)
 Cells maintain an imbalance of ions across the plasma membrane, which
cannot occur by either simple or facilitated diffusion.
 Gradients are generated by active transport.
 Coupled energy input is needed like ATP hydrolysis, absorbance of light,
electron transport, or the flow of other substances down their gradients.
Na+
K+
Cl–
Ca2+
H+

Extracellular
concentration
150 mM
5 mM
120 mM
10–3 M
10–7.4
(pH of 7.4)

Intracellular
concentration
10 mM
140 mM
10 mM
10–7 M
10–7.2
(pH of 7.2)

Ion Concentrations Inside and Outside a Typical Mammalian Cell
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Ionic gradient
15x
28x
12x
10,000x
Nearly 2x

4.6 | Active Transport (2 of 5)
Primary Active Transport: Coupling Transport to ATP Hydrolysis

 The Na+/K+ ATPase (sodium-potassium pump)requires K+ outside, Na+
inside, and is inhibited by ouabain.
 The ratio of Na+:K+ pumped is 3:2.
 The ATPase is a P-type pump, in which phosphorylation causes changes
in conformation and ion affinity that allow transport against gradients.
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4.6 | Active Transport (3 of 5)
Primary Active Transport: Coupling Transport to ATP Hydrolysis
 E1 conformation: Ion binding
sites are accessible to the inside
of the cell.
 E2 conformation: Ion binding
sites are accessible to the outside
of the cell.
 The sodium–potassium pump is
found only in animal cells.

The Na+/K+-ATPase pump: A model of the
E2 conformation
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4.6 | Active Transport (4 of 5)
Other Primary Ion Transport Systems
 The best studied P-type pump is the Ca2+-ATPase, present in the ER to
actively transport Ca2+ out of the cytosol into the lumen of this organelle.
 V-type pumps actively transport H+ across the walls of cytoplasmic
organelles.
 A V-type pump in the plasma membranes of kidney tubules helps
maintain the body's acid–base balance by secreting protons into the
forming urine.

Copyright ©2020 John Wiley & Sons, Inc.

4.6 | Active Transport (5 of 5)
Other Primary Ion Transport Systems
 The stomach contains the P-type pump.
 The stomach also has H/K-ATPase, which secretes a solution of
concentrated acid.

Control of acid secretion in the stomach
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4.6 | The Human Perspective (1 of 2)
Defects in Ion Channels and Transporters as a Cause of Inherited Disease

 Several inherited disorders have
been linked to mutations in
genes encoding ion proteins
channels.
 Cystic fibrosis (CF) is a genetic
disease characterized by
abnormal fluid secretions from
tissues and caused by a defective
chloride channel.

Effects on lung function from the absence
of the CFTR protein
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4.6 | The Human Perspective (2 of 2)
Defects in Ion Channels and Transporters as a Cause of Inherited Disease
Inherited disorder

Type of channel

Gene

Clinical consequences

Familial hemiplegic migraine (FHM)

Ca2+

CACNL1A4

Migraine headaches

Episodic ataxia type-2 (EA-2)

Ca

2+

CACNL1A4

Ataxia (lack of balance and coordination)

Hypokalemic periodic paralysis

Ca2+

CACNL1A3

Periodic myotonia (muscle stiffness) and
paralysis

Episodic ataxia type-1

K+

KCNA1

Ataxia

Benign familial neonatal convulsions

K+

KCNQ2

Epileptic convulsions

Nonsyndromic dominant deafness

K

KCNQ4

Deafness

Long QT syndrome

K+
Na+

HERG, KCNQ1, or
SCN5A

Dizziness and sudden death from ventricular
fibrillation

Hyperkalemic periodic paralysis

Na+

SCN4A

Periodic myotonia and paralysis

Liddle syndrome

Na+

B-ENaC

Hypertension (high blood pressure)

Myasthenia gravis

Na

nAChR

Muscle weakness

Dent's disease

Cl–

CLCN5

Kidney stones

Myotonia congenita

Cl–

CLC-1

Periodic myotonia

Bartter's syndrome type IV

Cl–

CLC-Kb

Kidney dysfunction and deafness

Cystic fibrosis

Cl–

CFTR

Lung congestion and infections

Cardiac arrhythmias

Na+
K+
Ca2+

Many different genes

Irregular or rapid heartbeat

+

+

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4.14 | Active Transport (1 of 2)
Co-Transport: Coupling Transport to Existing Ion Gradients
 Potential energy stored in ionic
gradients is utilized to perform
work,.
 Na+ concentration is kept low by
a Na+/K+-ATPase pump.
 Diffusion of sodium ions down a
concentration gradient drives the
cotransport of glucose.

Secondary transporter: the Na+ gradient
helps to transport glucose by a Na+/glucose
co-transporter
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4.14 | Active Transport (2 of 2)
Co-Transport: Coupling Transport to Existing Ion Gradients
 Secondary active transport
of glucose is an example of
symport.
 Antiporters or exchangers
move two transported
species in opposite
directions.
 During the transport cycle,
the protein's binding sites
gain alternating access to
the cytoplasm.

Secondary transporter: the Na+ gradient helps
to transport leucine into bacteria

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4.7 | Membrane Potentials and Nerve Impulses
(1 of 2)
 Potential differences exist when
charges are separated.
 Neurons are specialized cells for
information transmission using
changes in membrane potentials.
 Dendrites receive incoming
information; the cell body
contains the nucleus and
metabolic center of the cell; the
axon is a long extension for
conducting outgoing impulses.
(top) The structure of a nerve cell;
(bottom) A composite micrograph of one
rat hippocampal neuron
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4.7 | Membrane Potentials and Nerve Impulses
(2 of 2)
The Resting Potential
 The resting potential is the
membrane potential of a nerve
or muscle cell, subject to changes
when activated.
 K+ gradients maintained by the
Na+/K+-ATPase are responsible for
the resting potential.

Measuring a membrane's resting potential
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4.16 | Membrane Potentials
The Action Potential
 When cells are stimulated,
Na+ channels open, causing
membrane depolarization.
 When cells are stimulated,
voltage-gated Na+ channels
open, triggering the action
potential.
 Excitable membranes exhibit
all-or-none behavior.

Formation of an action potential
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4.17 | Propagation of Action Potentials as an
Impulse (1 of 2)
 APs produce local
membrane currents
depolarizing adjacent
membrane regions.
 Once triggered, a
succession of action
potentials passes down
the entire length of the
neuron without any loss
of intensity.

Propagation of an impulse results from the local flow
of ions unidirectionally

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