5
Cell Membranes and
Signaling
Chapter 5 Cell Membranes and Signaling
Key Concepts
5.1 Biological Membranes Have a Common
Structure and Are Fluid
5.2 Passive Transport across Membranes
Requires No Input of Energy
5.3 Active Transport Moves Solutes against Their
Concentration Gradients
5.4 Large Molecules Cross Membranes via
Vesicles
Chapter 5 Cell Membranes and Signaling
5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
5.6 Signal Transduction Allows the Cell to
Respond to Its Environment
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 design of membranes is known as
the fluid mosaic model.
Phospholipids form a continuous bilayer which
is like a “lake” in which a variety of proteins
“float.”
Figure 5.1 Membrane Structure
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
The lipid molecules are usually phospholipids
with two regions:
• Hydrophilic regions—electrically charged
“heads” associate with water molecules
• Hydrophobic regions—nonpolar fatty acid
“tails” that do not dissolve in water
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
A bilayer is formed when the fatty acid “tails”
associate with each other and the polar
“heads” face the aqueous environment.
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
Membranes may differ in lipid composition; there
are many types of phospholipids.
Phospholipids may differ in:
• Fatty acid chain length
• Degree of saturation
• Kinds of polar groups present
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
Cholesterol is an important component of animal
cell membranes.
Hydroxyl groups interact with the polar heads of
phospholipids.
Cholesterol is important in modulating
membrane fluidity; other steroids function as
hormones.
In-Text Art, Chapter 5, p. 84 (2)
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
The fatty acids make the membrane somewhat
fluid. This allows some molecules to move
laterally within the membrane.
Membrane fluidity is influenced by:
• Lipid composition—short, unsaturated
chains increase fluidity
• Temperature—fluidity decreases in colder
conditions
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
All biological membranes contain proteins; the
ratio of proteins to phospholipids varies.
Peripheral membrane proteins lack
hydrophobic groups and are not embedded in
the bilayer.
Integral membrane proteins are at least partly
embedded in the phospholipid bilayer.
In-Text Art, Chapter 5, p. 85
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
Anchored membrane proteins have hydrophobic
lipid components that anchor them in the
bilayer.
Proteins are asymmetrically distributed on the
inner and outer membrane surfaces.
Transmembrane proteins extend through the
bilayer; they may have domains with different
functions on the inner and outer sides of the
membrane.
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
Some membrane proteins can move within the
phosopholipid bilayer; others are restricted.
• Cell fusion experiments illustrate this
migration.
Proteins inside the cell can restrict movement of
membrane proteins, as can attachments to the
cytoskeleton.
Figure 5.2 Rapid Diffusion of Membrane Proteins (Part 1)
Figure 5.2 Rapid Diffusion of Membrane Proteins (Part 2)
Figure 5.2 Rapid Diffusion of Membrane Proteins (Part 3)
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
Diverse carbohydrates are located on the outer
cell membrane and play a role in
communication.
• Glycolipid—carbohydrate covalently
bonded to a lipid
• Glycoprotein—one or more
oligosaccharides covalently bonded to a
protein
• Proteoglycan—protein with more and
longer carbohydrates bonded to it
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
Cells can adhere to one another through
interactions between cell surface
carbohydrates and proteins.
Concept 5.1 Biological Membranes Have a Common Structure
and Are Fluid
Membranes are constantly 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 Passive Transport across Membranes Requires No
Input of Energy
Selective permeability: biological membranes
allow some substances, but not others, to
pass
Two processes of transport across
membranes:
1. Passive transport does not require
metabolic energy.
•
A substance moves down its
concentration gradient.
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
2. Active transport does require input of
metabolic energy.
•
A substance moves against its
concentration gradient.
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Passive transport can occur by:
• Simple diffusion through the phospholipid
bilayer
• Facilitated diffusion through channel
proteins or aided by carrier proteins
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Diffusion is the process of random movement
toward equilibrium; a net movement from
regions of greater concentration to regions of
lesser concentration.
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
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.
• Concentration gradient—the greater the
concentration gradient, the faster a
substance will diffuse.
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Cell cytoplasm is an aqueous solution, as is the
surrounding environment.
Diffusion of each solute depends only on its
own concentration.
A higher concentration inside the cell causes
the solute to diffuse out; higher concentration
outside causes the solute to diffuse in.
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Some molecules cross the phospholipid bilayer
by simple diffusion:
• O2, CO2, and small, nonpolar, lipid-soluble
molecules.
Polar (hydrophilic) molecules do not pass
through—they are not soluble in the
hydrophobic interior of the membrane.
• Amino acids, sugars, ions, water
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Osmosis is the diffusion of water across
membranes through special channels.
It depends on the concentration of water
molecules on either side of the membrane—
water moves down its concentration gradient.
The higher the total solute concentration, the
lower the concentration of water molecules.
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Osmotic pressure: pressure that must be
applied to a solution to prevent flow of water
across a membrane by osmosis
Π = cRT
c = total solute concentration
R = the gas constant
T = absolute temperature
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
The higher concentration of a substance on
one side of a membrane represents stored
energy.
If a membrane allows water, but not solutes, to
pass through, the net movement of water
molecules will be toward the solution with the
higher solute concentration and the lower
concentration of water molecules.
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
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 Shapes of Cells
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Concentration of solutes in the environment
determines the direction of osmosis in all
animal cells.
In other organisms, cell walls limit the volume
of water 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.
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Facilitated diffusion:
Channel proteins are integral membrane
proteins that form channels across the
membrane through which some substances
can pass.
Substances can also bind to carrier proteins
to speed up diffusion.
Both processes operate in either direction.
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Ion channels: channel proteins that allow
specific ions to pass through
Most are gated channels—they open when a
stimulus causes the protein to change shape.
• Ligand-gated—the stimulus is a ligand, a
chemical signal.
• Voltage-gated—the stimulus is a change in
electrical charge difference across the
membrane.
Figure 5.4 A Ligand-Gated Channel Protein Opens in Response to a Stimulus
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Water crosses membranes at a faster rate than
simple diffusion.
It may “hitchhike” with ions such as Na+ as
they pass through ion channels.
Aquaporins are channels that allow large
amounts of water to move along its
concentration gradient.
Figure 5.5 Aquaporins Increase Membrane Permeability to Water (Part 1)
Figure 5.5 Aquaporins Increase Membrane Permeability to Water (Part 2)
Figure 5.5 Aquaporins Increase Membrane Permeability to Water (Part 3)
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
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 (Part 1)
Concept 5.2 Passive Transport across Membranes Requires No
Input of Energy
Glucose is quickly broken down in the cell, so
there is always a strong concentration
gradient that favors glucose uptake.
But the system can become saturated—when
all of the carrier molecules are bound, the rate
of diffusion reaches a maximum.
Figure 5.6 A Carrier Protein Facilitates Diffusion (Part 2)
Concept 5.3 Active Transport Moves Solutes against Their
Concentration Gradients
Cells maintain an internal environment with a
different composition than the outside
environment.
This requires work—energy from ATP is
needed to move substances against their
concentration gradients (active transport).
Specific carrier proteins move substances in
only one direction, either into or out of the
cell.
Table 5.1
Concept 5.3 Active Transport Moves Solutes against Their
Concentration Gradients
Two types of active transport:
Primary active transport involves direct
hydrolysis of ATP for energy.
Secondary active transport uses the energy
from an ion concentration gradient or an
electrical gradient. The gradients are
established by primary active transport.
Concept 5.3 Active Transport Moves Solutes against Their
Concentration Gradients
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
Concept 5.3 Active Transport Moves Solutes against Their
Concentration Gradients
Secondary active transport uses energy that is
“regained” by letting ions move across the
membrane with their concentration gradients.
• Example: after the Na+–K+ pump
establishes a concentration gradient of
Na+, then passive diffusion of Na+ back into
the cell can provide energy for glucose
transport.
One protein usually moves both the ion and the
transported molecule across the membrane.
Concept 5.4 Large Molecules Cross Membranes via Vesicles
Macromolecules are too large or too charged to
pass through biological membranes, so
instead they cross within vesicles.
To take up or to secrete macromolecules, cells
must use endocytosis and exocytosis.
Concept 5.4 Large Molecules Cross Membranes via Vesicles
Exocytosis moves materials out of the cell in
vesicles.
The vesicle membrane fuses with the cell
membrane and the contents are released into
the environment.
Exocytosis is important in the secretion of
substances made by cells such as digestive
enzymes and neurotransmitters.
Concept 5.4 Large Molecules Cross Membranes via Vesicles
Endocytosis brings macromolecules and
particles into eukaryotic cells.
The cell membrane invaginates, or folds
around the particle and forms a vesicle.
The vesicle then separates from the
membrane.
Figure 5.8 Endocytosis and Exocytosis
Concept 5.4 Large Molecules Cross Membranes via Vesicles
Endocytosis depends on receptors—proteins
that bind to specific molecules (ligands).
The receptors are integral membrane proteins
on the cell membrane.
The resulting vesicle includes both the receptor
and its ligand, plus other substances present
near the site of invagination.
Concept 5.4 Large Molecules Cross Membranes via Vesicles
Phagocytosis (“cellular eating”): a specialized
cell engulfs a large particle or another cell
• A food vesicle (phagosome) forms and
usually fuses with a lysosome, where the
contents are digested.
Pinocytosis (“cellular drinking”): vesicles are
smaller and bring in fluids and dissolved
substances
Concept 5.4 Large Molecules Cross Membranes via Vesicles
Receptor endocytosis brings specific large
molecules into a cell via specific receptors.
This allows cells to control internal processes
by controlling location and abundance of each
type of receptor on the cell membrane.
It also plays a role in cell signaling.
Concept 5.4 Large Molecules Cross Membranes via Vesicles
The receptors are located in membrane regions
called coated pits.
The cytoplasmic surface of a pit is coated by
another protein (often clathrin).
When receptors bind to their ligands, the
coated pit invaginates and forms a coated
vesicle.
Clathrin stabilizes the vesicle.
Figure 5.9 Receptor Endocytosis
Concept 5.4 Large Molecules Cross Membranes via Vesicles
Once inside, the vesicle loses its clathrin coat
and fuses with a membrane-enclosed
compartment called an endosome.
Receptors may be recycled to the cell
membrane or degraded in a lysosome. This is
an important mechanism for controlling the
abundance of each kind of receptor on the
cell surface.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
Cell signaling: cells can process information
from their environment
Signals include physical stimuli, such as heat
or light, and chemicals (ligands). The cell
must have a receptor for the signal in order to
respond.
Following receptor activation by a signal, a
signal transduction pathway is initiated—a
sequence of events that lead to a cellular
response.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
In a multicellular animal, cells are exposed to
many chemical signals:
• Autocrine signals affect the same cells
that release them.
• Paracrine signals diffuse to and affect
nearby cells.
• Juxtacrine signaling requires direct
contact between the signaling and
responding cell.
• Hormones travel to distant cells.
Figure 5.10 Chemical Signaling Concepts
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
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
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
Signal transduction pathways often include
allosteric regulation:
• Protein shape changes as a result of a
molecule binding at a site other than the
active site (e.g., a ligand-gated channel).
A signal transduction pathway may produce
short or long term responses.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
Receptors can be classified by their location:
• Intracellular receptors are located inside
a cell. Their ligands are small or nonpolar
and can diffuse across the membrane.
• Membrane receptors located on the cell
surface have large or polar ligands that
cannot diffuse through the membrane.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
Membrane receptors:
• A chemical ligand fits into a 3-D site on the
receptor protein.
• The receptor may have a catalytic domain
on the cytoplasmic side. The ligand is an
allosteric regulator—it exposes the active
site on the catalytic domain.
Figure 5.12 A Signal Binds to Its Receptor
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
Ligand-receptor binding is noncovalent and
reversible.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
Reversible binding is important because cells
need to stop responding to a signal after the
appropriate response has occurred.
Inhibitors, or antagonists, can bind in place of
the normal ligand.
• Caffeine binds to receptors in the brain,
preventing binding by the normal ligands.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
Ion channel receptors are ligand-gated ion
channels; they change shape when a ligand
binds.
• Acetylcholine receptors on skeletal muscle
cells bind acetylcholine to open the
channel and allow Na+ to diffuse into the
cell.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
Protein kinase receptors also change shape
when a ligand binds.
The new shape exposes or activates a
cytoplasmic domain that has protein kinase
activity—it modifies proteins by adding
phosphate groups.
(Not all protein kinases are receptors.)
Figure 5.13 A Protein Kinase Receptor
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
G protein–linked receptors: ligand binding on
the surface exposes a site on the cytoplasmic
side that binds to a mobile membrane protein,
a G protein
The G protein is partially inserted in the lipid
bilayer and partially exposed on the
cytoplasmic surface.
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
Many G proteins have three subunits and can
bind three different molecules:
• The receptor
• GDP and GTP, used for energy transfer
• An effector protein that causes an effect in
the cell
Concept 5.5 The Membrane Plays a Key Role in a Cell’s
Response to Environmental Signals
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.
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, mediated by a signal
transduction pathway.
Signaling can initiate a cascade of protein
interactions—the initial signal is amplified and
distributed to cause different responses,
ultimately leading to changes in cell function.
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
There are many ways in which cells respond to
environmental signals:
• Opening of ion channels—changes the
balance of ion concentrations between the
outside and inside of the cell and results in
change in the electrical potential across
the membrane.
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
• Alterations in gene expression—genes
may be switched on (upregulated) or
switched off (downregulated). This affects
the abundance of proteins (often
enzymes), thus changing cell function.
• Alteration of enzyme activities—more rapid
response than those involving change in
gene expression.
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
The same signal can lead to different
responses in different types of cells.
Example: Heart and digestive tract muscle cells
respond differently to epinephrine because
the signal transduction pathways stimulated
are different in the two cell types.
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
Often there is a small molecule intermediary, a
“second messenger,” between the activated
receptor and the cascade of responses that
ensues.
In the fight-or-flight response, epinephrine
(adrenaline) activates the liver enzyme
glycogen phosphorylase, which catalyzes
breakdown of glycogen for quick energy.
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
Researchers found that glycogen
phosphorylase could be activated by
membrane-bound 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 (Part 1)
Figure 5.15 The Discovery of a Second Messenger (Part 2)
Figure 5.15 The Discovery of a Second Messenger (Part 3)
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
The second messenger was later discovered to
be cyclic AMP (cAMP).
Second messengers regulate target enzymes
by binding to them noncovalently.
They 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.
Figure 5.16 The Formation of Cyclic AMP
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
Signal transduction pathways involve multiple
steps in which enzymes are either activated
or inhibited by other enzymes.
In liver cells, a signal cascade begins when
epinephrine stimulates a G protein–mediated
protein kinase pathway.
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
cAMP is produced and activates protein kinase
A, which phosphorylates two other enzymes,
with opposite effects:
• Inhibition—glycogen synthase is
inactivated by phosphorylation, which
prevents glucose storage.
• Activation—phosphorylase kinase is
phosphorylated and starts a cascade that
results in the liberation of glucose
molecules from glycogen.
Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 1)
Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
The original signal is amplified at every step in
the cascade.
Each molecule of epinephrine that arrives at
the cell membrane ultimately results in 10,000
molecules of blood glucose.
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
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
ultimate response.
Figure 5.18 Signal Transduction Regulatory Mechanisms
Concept 5.6 Signal Transduction Allows the Cell to Respond to
Its Environment
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
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