Principles of Life
Hillis • Sadava • Heller • Price
Instructor’s Manual
Chapter 5: Cell Membranes and Signaling
OVERVIEW
Chapter 5 examines the structure and functions of cell membranes, describing the fluid
mosaic model and the lipid and protein classes that account for the membrane’s
properties. After covering the key concepts of diffusion, the ion channel and membrane
transporter proteins are introduced, with emphasis on passive and active transport
mechanisms. The role of the membrane in the cell’s response to signals and the different
kinds of membrane receptors are described. Elements of a signal transduction pathway
and ways in which a cell may respond through signal transduction and second
messengers are also described.
KEY CONCEPTS/CHAPTER OUTLINE
5.1 Biological Membranes Have a Common Structure and Are Fluid
 Lipids form the hydrophobic core of the membrane
 Membrane proteins are asymmetrically distributed
 Plasma membrane carbohydrates are recognition sites
 Membranes are constantly changing
Biological membranes are bilayered, dynamic structures that perform vital physiological
roles, form cell boundaries and regulate movement in and out of cells. These tasks are
made possible by various combinations of lipids, proteins, and carbohydrates.
5.2 Some Substances Can Cross the Membrane by Diffusion
 Diffusion is the process of random movement toward a state of equilibrium
 Simple diffusion takes place through the phospholipid bilayer
 Osmosis is the diffusion of water across membranes
 Diffusion may be aided by channel proteins
 Carrier proteins aid diffusion by binding substances
Substances can diffuse across a membrane by three processes: unaided diffusion through
the phospholipid bilayer, diffusion through protein channels, or diffusion by means of a
carrier protein (facilitated diffusion).
5.3 Some Substances Require Energy to Cross the Membrane
 Active transport is directional
 Different energy sources distinguish different active transport systems
Active transport requires the use of energy to move substances across a membrane
against a concentration gradient via specialized proteins.
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5.4 Large Molecules Cross the Membrane via Vesicles
 Macromolecules and particles enter the cell by endocytosis
 Receptor-mediated endocytosis is specific
 Exocytosis moves materials out of the cell
Macromolecules and particles pass into a cell through endocytosis, which may be
receptor–mediated. These substances leave the cell through exocytosis.
5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental
Signals
 Cells are exposed to many signals and may have different responses
 Membrane proteins act as receptors
 Receptors can be classified by location and function
A signal transduction pathway involves the signal received by a cell, the receptor for that
signal, and the varied responses the cell can have. Membrane proteins act as receptors
and are classified by location and function, such as ion channel receptors, protein kinase
receptors, and G protein–linked receptors.
5.6 Signal Transduction Allows the Cell to Respond to Its Environment
 Second messengers can stimulate signal transduction
 A signaling cascade involves enzyme regulation and signal amplification
 Signal transduction is highly regulated
 Cell function changes in response to environmental signals
Second messengers can distribute a signal and amplify it by stimulating a signaling
cascade that involves inhibition or activation of enzymes. Signal transduction is highly
regulated as it leads to changes in cell functions.
LECTURE OUTLINE
Chapter 5 Opening Question
What role does the cell membrane play in the body’s response to caffeine?
Concept 5.1 Biological Membranes Have a Common Structure and Are
Fluid
A membrane’s structure and functions are determined by its constituents: lipids, proteins,
and carbohydrates.
The general structure of membranes is known as the fluid mosaic model.
Phospholipids form a bilayer which is like a “lake” in which a variety of proteins “float.”
(VIDEO 5.1 Cell Visualization: Membranes, hormones, and receptors)
FIGURE 5.1 Membrane Molecular Structure
Lipids form the hydrophobic core of the membrane.
Most lipid molecules are phospholipids with two regions:
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• Hydrophilic regions—electrically charged “heads” that associate with water molecules
• Hydrophobic regions—nonpolar fatty acid “tails” that do not dissolve in water
A bilayer is formed when the fatty acid “tails” associate with each other and the polar
“heads” face the aqueous environment.
Bilayer organization helps membranes fuse during vesicle formation and phagocytosis.
(LINK Review the properties of phospholipid bilayers in Concept 2.4)
Membranes may differ in lipid composition as there are many types of phospholipids.
• Phospholipids may differ in:
• Fatty acid chain length
• Degree of saturation
• Kinds of polar groups present
Two important factors in membrane fluidity:
• Lipid composition—types of fatty acids can increase or decrease fluidity
• Temperature—membrane fluidity decreases in colder conditions
(APPLY THE CONCEPT Biological membranes have a common structure and are fluid)
(INTERACTIVE TUTORIAL 5.1 Lipid Bilayer: Temperature Effects on Composition)
Biological membranes contain proteins, with varying ratios of phospholipids.
• Peripheral membrane proteins lack hydrophobic groups and are not embedded in the
bilayer.
• Integral membrane proteins are partly embedded in the phospholipid bilayer.
(See Figure 5.1)
Anchored membrane proteins have lipid components that anchor them in the bilayer.
Proteins are asymmetrically distributed on the inner and outer membrane surfaces.
A transmembrane protein extends through the bilayer on both sides, and may have
different functions in its external and transmembrane domains.
Some membrane proteins can move within the phosopholipid bilayer, while others are
restricted.
Proteins inside the cell can restrict movement of membrane proteins, as can attachments
to the cytoskeleton.
FIGURE 5.2 Rapid Diffusion of Membrane Proteins
Plasma membrane carbohydrates are located on the outer membrane and can serve as
recognition sites.
• Glycolipid—a carbohydrate bonded to a lipid
• Glycoprotein—a carbohydrate bonded to a protein
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Membranes are constantly changing by forming, transforming into other types, fusing,
and breaking down.
Though membranes appear similar, there are major chemical differences among the
membranes of even a single cell.
Concept 5.2 Some Substances Can Cross the Membrane by Diffusion
Biological membranes allow some substances, and not others, to pass. This is known as
selective permeability.
Two processes of transport:
• Passive transport does not require metabolic energy.
• Active transport requires input of metabolic energy.
Passive transport of a substance can occur through two types of diffusion:
• Simple diffusion through the phospholipid bilayer
• Facilitated diffusion through channel proteins or aided by carrier proteins
Diffusion is the process of random movement toward equilibrium.
Speed of diffusion depends on three factors:
• Diameter of the molecules—smaller molecules diffuse faster
• Temperature of the solution—higher temperatures lead to faster diffusion
• The concentration gradient in the system—the greater the concentration gradient in a
system, the faster a substance will diffuse
A higher concentration inside the cell causes the solute to diffuse out, and a higher
concentration outside causes the solute to diffuse in, for many molecules.
Simple diffusion takes place through the phospholipid bilayer.
A molecule that is hydrophobic and soluble in lipids can pass through the membrane.
Polar molecules do not pass through—they are not soluble in the hydrophilic interior and
form bonds instead in the aqueous environment near the membrane.
Osmosis is the diffusion of water across membranes.
It depends on the concentration of solute molecules on either side of the membrane.
Water passes through special membrane channels.
When comparing two solutions separated by a membrane:
• A hypertonic solution has a higher solute concentration.
• Isotonic solutions have equal solute concentrations.
• A hypotonic solution has a lower solute concentration.
FIGURE 5.3 Osmosis can Modify the Shape of Cells
The concentration of solutes in the environment determines the direction of osmosis in all
animal cells.
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In other organisms, cell walls limit the volume that can be taken up.
Turgor pressure is the internal pressure against the cell wall—as it builds up, it prevents
more water from entering.
Diffusion may be aided by channel proteins.
Channel proteins are integral membrane proteins that form channels across the
membrane.
Substances can also bind to carrier proteins to speed up diffusion.
Both are forms of facilitated diffusion.
Ion channels are a type of channel protein—most are gated, and can be opened or closed
to ion passage.
A gated channel opens when a stimulus causes the channel to change shape.
The stimulus may be a ligand, a chemical signal.
A ligand-gated channel responds to its ligand.
A voltage-gated channel opens or closes in response to a change in the voltage across the
membrane.
FIGURE 5.4 A Ligand-Gated Channel Protein Opens in Response to a Stimulus
Water crosses membranes at a faster rate than simple diffusion.
It may “hitchhike” with ions such as Na+ as they pass through channels.
Aquaporins are specific channels that allow large amounts of water to move along its
concentration gradient.
FIGURE 5.5 Aquaporins Increase Membrane Permeability to Water
Carrier proteins in the membrane facilitate diffusion by binding substances.
Glucose transporters are carrier proteins in mammalian cells.
Glucose molecules bind to the carrier protein and cause the protein to change shape—it
releases glucose on the other side of the membrane.
FIGURE 5.6 A Carrier Protein Facilitates Diffusion
Transport by carrier proteins differs from simple diffusion, though both are driven by the
concentration gradient.
The facilitated diffusion system can become saturated—when all of the carrier molecules
are bound, the rate of diffusion reaches its maximum.
(ANIMATED TUTORIAL 5.1 Passive Transport)
Concept 5.3 Some Substances Require Energy to Cross the Membrane
Active transport requires the input of energy to move substances against their
concentration gradients.
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Active transport is used to overcome concentration imbalances that are maintained by
proteins in the membrane.
TABLE 5.1 Membrane Transport Mechanisms
(ANIMATED TUTORIAL 5.1 Passive Transport)
The energy source for active transport is often ATP.
Active transport is directional and moves a substance against its concentration gradient.
A substance moves in the direction of the cell’s needs, usually by means of a specific
carrier protein.
Two types of active transport:
• Primary active transport involves hydrolysis of ATP for energy.
• Secondary active transport uses the energy from an ion concentration gradient, or an
electrical gradient.
The sodium–potassium (Na+–K+) pump is an integral membrane protein that pumps
Na+ out of a cell and K+ in.
One molecule of ATP moves two K+ and three Na+ ions.
FIGURE 5.7 Primary Active Transport: The Sodium–Potassium Pump
Secondary active transport uses energy that is “regained,” by letting ions move across the
membrane with their concentration gradients.
Secondary active transport may begin with passive diffusion of a few ions, or may
involve a carrier protein that transports both a substance and ions.
(ANIMATED TUTORIAL 5.2 Active Transport)
Concept 5.4 Large Molecules Cross the Membrane via Vesicles
Macromolecules are too large or too charged to pass through biological membranes and
instead pass through vesicles.
To take up or to secrete macromolecules, cells must use endocytosis or exocytosis.
FIGURE 5.8 Endocytosis and Exocytosis
Three types of endocytosis brings molecules into the cell: phagocytosis, pinocytosis, and
receptor–mediated endocytosis.
In all three, the membrane invaginates, or folds around the molecules and forms a
vesicle.
The vesicle then separates from the membrane.
In phagocytosis (“cellular eating”), part of the membrane engulfs a large particle or cell.
A food vacuole (phagosome) forms and usually fuses with a lysosome, where contents
are digested.
(LINK Review the discussion of phagocytosis in Concept 4.3)
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In pinocytosis (“cellular drinking”), vesicles also form.
The vesicles are smaller and bring in fluids and dissolved substances, as in the
endothelium near blood vessels.
(VIDEO 5.2 Pinocytosis and membrane ruffling in a mouse epithelial cell)
Receptor–mediated endocytosis depends on receptors to bind to specific molecules
(their ligands).
The receptors are integral membrane proteins located in regions called coated pits.
The cytoplasmic surface is coated by another protein (often clathrin).
When receptors bind to their ligands, the coated pit invaginates and forms a coated
vesicle.
The clathrin stabilizes the vesicle as it carries the macromolecules into the cytoplasm.
Once inside, the vesicle loses its clathrin coat and the substance is digested.
(APPLY THE CONCEPT Some substances require energy to cross the membrane)
(VIDEO 5.3 Cell Visualization: Endocytosis)
FIGURE 5.9 Receptor–Mediated Endocytosis
Exocytosis moves materials out of the cell in vesicles.
The vesicle membrane fuses with the plasma membrane and the contents are released into
the cellular environment.
Exocytosis is important in the secretion of substances made in the cell.
(ANIMATED TUTORIAL 5.3 Endocytosis and Exocytosis)
(VIDEO 5.4 Exocytosis of coccoliths in a marine golden alga, Pleurochrysis)
Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to
Environmental Signals
Cells can respond to many signals if they have a specific receptor for that signal.
A signal transduction pathway is a sequence of molecular events and chemical
reactions that lead to a cellular response, following the receptor’s activation by a signal.
Cells are exposed to many signals and may have different responses:
• Autocrine signals affect the same cells that release them.
• Paracrine signals diffuse to and affect nearby cells.
• Hormones travel to distant cells.
FIGURE 5.10 Chemical Signaling Concepts
Only cells with the necessary receptors can respond to a signal—the target cell must be
able to sense it and respond to it.
A signal transduction pathway involves a signal, a receptor, and a response.
FIGURE 5.11 Signal Transduction Concepts
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A common mechanism of signal transduction is allosteric regulation.
This involves an alteration in a protein’s shape as a result of a molecule binding to it.
A signal transduction pathway may produce short or long term responses.
(See Figure 5.6)
A signal molecule, or ligand, fits into a three-dimensional site on the receptor protein.
Binding of the ligand causes the receptor to change its three-dimensional shape.
The change in shape initiates a cellular response.
FIGURE 5.12 A Signal Binds to Its Receptor
Ligands are generally not metabolized further, but their binding may expose an active site
on the receptor.
Binding is reversible and the ligand can be released, to end stimulation.
An inhibitor, or antagonist, can bind in place of the normal ligand.
(See Figure 5.6)
Receptors can be classified by their location in the cell.
This is determined by whether or not their ligand can diffuse through the membrane.
(VIDEO 5.5 Cell Visualization: Signals and calcium)
Cytoplasmic receptors have ligands, such as estrogen, that are small or nonpolar and can
diffuse across the membrane.
Membrane receptors have large or polar ligands, such as insulin, that cannot diffuse and
must bind to a transmembrane receptor at an extracellular site.
Receptors are also classified by their activity:
• Ion channel receptors
• Protein kinase receptors
• G protein–linked receptors
(VIDEO 5.5 Cell Visualization: Signals and calcium)
Ion channel receptors, or gated ion channels, change their three-dimensional shape
when a ligand binds.
The acetylcholine receptor, a ligand-gated sodium channel, binds acetylcholine to open
the channel and allow Na+ to diffuse into the cell.
(LINK Nerve cells communicate with muscle cells at neuromuscular junctions, which are
described in Concept 34.X)
(See Figure 5.4)
Protein kinase receptors change their shape when a ligand binds.
The new shape exposes or activates a cytoplasmic domain that has catalytic (protein
kinase) activity.
FIGURE 5.13 A Protein Kinase Receptor
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Protein kinases catalyze the following reaction:
ATP + protein  ADP + phosphorylated protein
Each protein kinase has a specific target protein, whose activity is changed when it is
phosphorylated.
Ligands binding to G protein–linked receptors expose a site that can bind to a
membrane protein, a G protein.
The G protein is partially inserted in the lipid bilayer, and partially exposed on the
cytoplasmic surface.
Many G proteins have three subunits and can bind three molecules:
• The receptor
• GDP and GTP, used for energy transfer
• An effector protein to cause an effect in the cell
The activated G protein–linked receptor exchanges a GDP nucleotide bound to the G
protein for a higher energy GTP.
The activated G protein activates the effector protein, leading to signal amplification.
(ANIMATED TUTORIAL 5.4 G Protein–Linked Signal Transduction and Cancer)
FIGURE 5.14 A G Protein–Linked Receptor
Concept 5.6 Signal Transduction Allows the Cell to Respond to Its
Environment
Signal activation of a specific receptor leads to a cellular response, which is mediated by
a signal transduction pathway.
Signaling can initiate a cascade of protein interactions—the signal can then be amplified
and distributed to cause different responses.
(VIDEO 5.6 Chemotaxis of human neutrophils)
A second messenger is an intermediary between the receptor and the cascade of
responses.
In the fight-or-flight response, epinephrine (adrenaline) activates the liver enzyme
glycogen phosphorylase.
The enzyme catalyzes the breakdown of glycogen to provide quick energy.
Researchers found that the cytoplasmic enzyme could be activated by the membranebound epinephrine in broken cells, as long as all parts were present.
They discovered that another molecule delivered the message from the “first messenger,”
epinephrine, to the enzyme.
FIGURE 5.15 The Discovery of a Second Messenger
The second messenger was later discovered to be cyclic AMP (cAMP).
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Second messengers allow the cell to respond to a single membrane event with many
events inside the cell—they distribute the signal.
They amplify the signal by activating more than one enzyme target.
(LINK Review enzyme regulation in Concept 3.4)
FIGURE 5.16 The Formation of Cyclic AMP
Signal transduction pathways involve multiple steps—enzymes may be either activated or
inhibited by other enzymes.
In liver cells, a signal cascade begins when epinephrine stimulates a G protein–mediated
protein kinase pathway.
Epinephrine binds to its receptor and activates a G protein.
cAMP is produced and activates protein kinase A—it phosphorylates two other enzymes,
with opposite effects:
• Inhibition
• Activation
FIGURE 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity
• Inhibition—protein kinase A inactivates glycogen synthase through phosphorylation,
and prevents glucose storage.
• Activation—Phosphorylase kinase is activated when phosphorylated and is part of a
cascade that results in the liberation of glucose molecules.
(ANIMATED TUTORIAL 5.5 Signal Transduction Pathway)
(See Figure 5.17, step 1)
(See Figure 5.17, steps 2 and 3)
Signal transduction ends after the cell responds—enzymes convert each transducer back
to its inactive precursor.
The balance between the regulating enzymes and the signal enzymes determines the
cell’s response.
FIGURE 5.18 Signal Transduction Regulatory Mechanisms
Cells can alter the balance of enzymes in two ways:
• Synthesis or breakdown of the enzyme
• Activation or inhibition of the enzymes by other molecules
Cell functions change in response to environmental signals:
• Opening of ion channels
• Alterations in gene expression
• Alteration of enzyme activities
(VIDEO 5.7 Calcium waves in brain glial cells)
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(See Figure 5.4)
(See Figure 5.17)
Answer to Opening Question
Caffeine is a large, polar molecule that binds to receptors on nerve cells in the brain.
Its structure is similar to adenosine, which binds to receptors after activity or stress and
results in drowsiness.
Caffeine binds to the same receptor, but does not activate it—the result is that the person
remains alert.
FIGURE 5.19 Caffeine and the Cell Membrane
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