LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY

Module 5
CELLULAR MEMBRANE STRUCTURE AND FUNCTION

Topics:

5:1 Membrane Structure and Dynamics

5.2 Pumps, Carriers, Channels

Time Frame: 5 hours

Introduction

Membranes composed of lipids and proteins form the barrier between each cell and
its environment. Membranes also partition the cytoplasm of eukaryotes into
compartments, including the nucleus and membrane-bounded organelles. Each type
of membrane is specialized for its various functions, but all biological membranes
have much in common: a planar fluid bilayer of lipid molecules, integral membrane
proteins that cross the lipid bilayer, and peripheral membrane proteins on both
surfaces.

Objectives:

 Describe the membrane structure and dynamics.

 Discuss how organelles interact and coordinate in maintaining the life of
organisms.
Teaching Strategies
 Explain and Activities:
the functions of membrane proteins and lipids and its effect to
membrane fluidity.


Pre-test

I. Multiple Choice. Encircle the letter of the best answer.

1. Which of the following is the protein located entirely outside of the lipid bilayer,
on either the cytoplasmic or extracellular side?
a. integral protein c. integrated protein
b. peripheral protein d. glycoprotein

2. Which of the following is not true about the phospholipid molecule?

a. Hydrophobic region c. amphipatic
b. b. hydrophillic region d. all are correct responses

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3. Which of the channels whose conformational state depends on mechanical

forces?
a. Voltage-gated channels c. Mechano-gated channels
b. Ligand-gated channel d. Osmosis channels

4. Which statement represents a notable difference between simple diffusion

and facilitated diffusion?
a. Unlike simple diffusion, facilitated diffusion can transport ligands against a
concentrate gradient.
b. Unlike simple diffusion, the rate of facilitated diffusion is limited by the
number of transport proteins in the membrane.
c. Unlike simple diffusion, facilitated diffusion requires energy in the form of
ATP.
d. Unlike simple diffusion, facilitated diffusion can occur in any type of cell.

5. Which of the following is not true about the plasma membrane?

a. protection c. energy
b. transport d. none of the above

6. Which intermolecular process primarily drives the formation of a bilayer when

phospholipids are added to water?
a. Lipids cause water to arrange in an ordered, unfavorable cage-like
structure. Forcing lipids into a bilayer reduces this effect.
b. Phospholipids self-assemble into a bilayer due to the strong affinity they
have for each other.
c. The ordered arrangement of a bilayer is more favorable than the
disordered state of individual free-floating phospholipids.
d. A bilayer arrangement maximizes the strength of Van der Waals forces
among phospholipids.

7. Which statement best describes how cholesterol affects cell membrane

fluidity?
a. Cholesterol increases fluidity at high temperatures and decreases fluidity
at low temperatures.
b. Cholesterol increases fluidity at high temperatures and increases fluidity at
low temperatures.
c. Cholesterol decreases fluidity at high temperatures and decreases fluidity
at low temperatures.
d. Cholesterol decreases fluidity at high temperatures and increases fluidity
at low temperatures.

8. Compared to a typical animal cell, the cell membranes on the paw of a polar
bear would most likely have an increased concentration of which
macromolecule?
a. Unsaturated phospholipids
b. Saturated phospholipids
c. Aquaporin proteins
d. Potassium channel proteins

9. Which molecule diffuses through a membrane most quickly?

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a. Ethylene
b. Urea
c. Glucose
d. Benzene

10. Glucose typically enters the cell through which mechanism?

a. Pinocytosis through a channel protein
b. Active transport by a glucose transport protein
c. Simple diffusion through the cell membrane
d. Facilitated diffusion through a carrier protein

(Choice D, Incorrect)

Learning Activities

5.1 Membrane Structure and dynamics

Cells are separated from the external world by a thin, fragile structure called the
plasma membrane that is only 5 to 10 nm wide. The plasma membrane, also known
as the cell surface membrane or plasmalemma, defines the boundary of the cell. It
would require about five thousand plasma membranes stacked one on top of the
other to equal the thickness of a single page of a book. Because it is so thin, no hint
of the plasma membrane is detected when a section of a cell is examined under a
light microscope. In fact, it wasn’t until the late 1950s that techniques for preparing
and staining tissue had progressed to the point where the plasma membrane could
be resolved in the electron microscope. These early electron micrographs, such as
those taken by J. D. Robertson of Duke University, portrayed the plasma membrane
as a three-layered structure, consisting of darkly staining inner and outer layers and
lightly staining middle layer. All membranes that were examined closely—whether
they were plasma, nuclear, or cytoplasmic membranes, or taken from plants,
animals, or microorganisms—showed this same ultrastructure. In addition to
providing a visual image of this critically important cellular structure, these electron
micrographs touched off a vigorous debate as to the molecular composition of the
various layers of a membrane, an argument that went to the very heart of the subject
of membrane structure and function.

Figure 24. Molecular View of Cell Membrane

([Link])

Functions of Plasma Membrane:

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1. Compartmentalization. Membranes are continuous, unbroken sheets and, as

such, inevitably enclose compartments. The plasma membrane encloses the
contents of the entire cell, whereas the nuclear and cytoplasmic membranes enclose
diverse intracellular spaces. The various membrane-bounded compartments of a cell
possess markedly different contents. Membrane compartmentalization allows
specialized activities to proceed without external interference and enables cellular
activities to be regulated independently of one another.

2. Scaffold for biochemical activities. Membranes not only enclose compartments

but are also a distinct compartment themselves. As long as reactants are present in
solution, their relative positions cannot be stabilized and their interactions are
dependent on random collisions. Because of their construction, membranes provide
the cell with an extensive framework or scaffolding within which components can be
ordered for effective interaction.

3. Providing a selectively permeable barrier. Membranes prevent the unrestricted

exchange of molecules from one side to the other. At the same time, membranes
provide the means of communication between the compartments they separate. The
plasma membrane, which encircles a cell, can be compared to a moat around a
castle: both serve as a general barrier, yet both have gated “bridges” that promote
the movement of select elements into and out of the enclosed living space.

4. Transporting solutes. The plasma membrane contains the machinery for

physically transporting substances from one side of the membrane to another, often
from a region where the solute is present at low concentration into a region where
that solute is present at much higher concentration. The membrane’s transport
machinery allows a cell to accumulate substances, such as sugars and amino acids,
that are necessary to fuel its metabolism and build its macromolecules. The plasma
membrane is also able to transport specific ions, thereby establishing ionic gradients
across itself. This capability is especially critical for nerve and muscle cells.

5. Responding to external signals. The plasma membrane plays a critical role in

the response of a cell to external stimuli, a process known as signal transduction.
Membranes possess receptors that combine with specific molecules (or ligands)
having a complementary structure. Different types of cells have membranes with
different receptors and are, therefore, capable of recognizing and responding to
different ligands in their environment. The interaction of a plasma membrane
receptor with an external ligand may cause the membrane to generate a signal that
stimulates or inhibits internal activities. For example, signals generated at the plasma
membrane may tell a cell to manufacture more glycogen, to prepare for cell division,
to move toward a higher concentration of a particular compound, to release calcium
from internal stores, or possibly to commit suicide.

6. Intercellular interaction. Situated at the outer edge of every living cell, the
plasma membrane of multicellular organisms mediates the interactions between a
cell and its neighbors. The plasma membrane allows cells to recognize and signal
one another, to adhere when appropriate, and to exchange materials and
information.

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7. Energy transduction. Membranes are intimately involved in the processes by

which one type of energy is converted to another type (energy transduction). The
most fundamental energy transduction occurs during photosynthesis when energy in
sunlight is absorbed by membrane-bound pigments, converted into chemical energy,
and stored in carbohydrates. Membranes are also involved in the transfer of
chemical energy from carbohydrates and fats to ATP. In eukaryotes, the machinery
for these energy conversions is contained within membranes of chloroplasts and
mitochondria.

History on Plasma Membrane Studies

The first insights into the chemical nature of the outer boundary layer of a cell were
obtained by Ernst Overton of the University of Zürich during the 1890s. Overton
knew that nonpolar solutes dissolved more readily in nonpolar solvents than in polar
solvents, and that polar solutes had the opposite solubility.

The first proposal that cellular membranes might contain a lipid bilayer was made in
1925 by two Dutch scientists, E. Gorter and F. Grendel. These researchers extracted
the lipid from human red blood cells and measured the amount of surface area the
lipid would cover when spread over the surface of water

Gorter and Grendel speculated that the actual ratio was 2:1 and concluded that the
plasma membrane contained a bimolecular layer of lipids, that is, a lipid bilayer
In 1935, Hugh Davson and James Danielli proposed that the plasma membrane was
composed of a lipid bilayer that was lined on both its inner and outer surface by a
layer of globular proteins. They revised their model in the early 1950s to account for
the selective permeability of the membranes they had studied.

Experiments conducted in the late 1960s led to a new concept of membrane

structure, as detailed in the fluidmosaic model proposed in 1972 by S. Jonathan
Singer and Garth Nicolson of the University of California, San Diego. In the fluid-
mosaic model, which has served as the “central dogma” of membrane biology for
more than three decades, the lipid bilayer remains the core of the membrane, but
attention is focused on the physical state of the lipid (Figure 25). Unlike previous
models, the bilayer of a fluid-mosaic membrane is present in a fluid state, and
individual lipid molecules can move laterally within the plane of the membrane. The
structure and arrangement of membrane proteins in the fluid-mosaic model differ
from those of previous models in that they occur as a “mosaic” of discontinuous
particles that penetrate the lipid sheet. Most importantly, the fluid-mosaic model
presents cellular membranes as dynamic structures in which the components are
mobile and capable of coming together to engage in various types of transient or
semipermanent interactions.

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Figure 25. Fluid-Mosaic Model of Cell Membrane

(Karp, 2013)

Self-Check
4.1
Answer substantially:
1. Describe some of the important roles of membranes in the life of a
eukaryotic cell. What do you think might be the effect of a membrane
that was incapable of performing one or another of these roles?

Chemical Composition of Membranes

Membranes are lipid–protein assemblies in which the components are held together
in a thin sheet by noncovalent bonds. The core of the membrane consists of a sheet
of lipids arranged in a bimolecular layer. The lipid bilayer serves primarily as a
structural backbone of the membrane and provides the barrier that prevents random
movements of water-soluble materials into and out of the cell. The proteins of the
membrane, on the other hand, carry out most of the specific functions. Each type of
differentiated cell contains a unique complement of membrane proteins, which
contributes to the specialized activities of that cell type. The ratio of lipid to protein in
a membrane varies, depending on the type of cellular membrane. The differences
can be correlated with the basic functions of these membranes. The inner
mitochondrial membrane contains the protein carriers of the electron-transport chain,
and relative to other membranes, lipid is diminished. In contrast, the myelin sheath

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acts primarily as electrical insulation for the nerve cell it encloses, a function that is
best carried out by a thick lipid layer of high electrical resistance with a minimal
content of protein. Membranes also contain carbohydrates, which are attached to the
lipids and proteins (Figure 26).

Membrane Lipids
Membranes contain a wide diversity of lipids, all of which are amphipathic; that is,
they contain both hydrophilic and hydrophobic regions. There are three main types of
membrane lipids: phosphoglycerides, sphingolipids, and cholesterol.

Phosphoglycerides
Most membrane lipids contain a phosphate group, which makes them
phospholipids. Because most membrane phospholipids are built on a glycerol
backbone, they are called phosphoglycerides. Unlike triglycerides, which have
three fatty acids and are not amphipathic, membrane glycerides are diglycerides—
only two of the hydroxyl groups of the glycerol are esterified to fatty acids; the third is
esterified to a hydrophilic phosphate group. Without any additional substitutions
beyond the phosphate and the two fatty acyl chains, the molecule is called
phosphatidic acid, which is virtually absent in most membranes. Instead, membrane
phosphoglycerides have an additional group linked to the phosphate, most
commonly either choline (forming phosphatidylcholine, PC), ethanolamine (forming
phosphatidylethanolamine, PE), serine (forming phosphatidylserine, PS), or inositol
(forming phosphatidylinositol, PI). Each of these groups is small and hydrophilic and,
together with the negatively charged phosphate to which it is attached, forms a
highly water-soluble domain at one end of the molecule, called the head group. At
physiologic pH, the head groups of PS and PI have an overall negative charge,
whereas those of PC and PE are neutral. In contrast, the fatty acyl chains are
hydrophobic, unbranched hydrocarbons approximately 16 to 22 carbons in length. A
membrane fatty acid may be fully saturated (i.e., lack double bonds),
monounsaturated (i.e., possess one double bond), or polyunsaturated (i.e., possess
more than one double bond). Phosphoglycerides often contain one unsaturated and
one saturated fatty acyl chain.

Recent interest has focused on the apparent health benefits of two highly
unsaturated fatty acids (EPA and DHA) found at high concentration in fish oil. EPA
and DHA contain five and six double bonds, respectively, and are incorporated
primarily into PE and PC molecules of certain membranes, most notably in the brain
and retina. EPA and DHA are described as omega-3 fatty acids because their last
double bond is situated 3 carbons from the omega (CH3) end of the fatty acyl chain.
With fatty acid chains at one end of the molecule and a polar head group at the other
end, all of the phosphoglycerides exhibit a distinct amphipathic character.

Sphingolipids
A less abundant class of membrane lipids, called sphingolipids, are derivatives of
sphingosine, an amino alcohol that contains a long hydrocarbon chain. Sphingolipids
consist of sphingosine linked to a fatty acid by its amino group. This molecule is a
ceramide. The various sphingosine-based lipids have additional groups esterified to
the terminal alcohol of the sphingosine moiety. If the substitution is
phosphorylcholine, the molecule is sphingomyelin, which is the only phospholipid of
the membrane that is not built with a glycerol backbone. If the substitution is a

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carbohydrate, the molecule is a glycolipid. If the carbohydrate is a simple sugar, the

glycolipid is called a cerebroside; if it is a small cluster of sugars, the glycolipid is
called a ganglioside. Since all sphingolipids have two long, hydrophobic hydrocarbon
chains at one end and a hydrophilic region at the other, they are also amphipathic
and basically similar in overall structure to the phosphoglycerides. Glycolipids are
interesting membrane components. Relatively little is known about them, yet
tantalizing hints have emerged to suggest they play crucial roles in cell function. The
nervous system is particularly rich in glycolipids.

Cholesterol
Another lipid component of certain membranes is the sterol cholesterol, which in
certain animal cells may constitute up to 50 percent of the lipid molecules in the
plasma membrane. Cholesterol is absent from the plasma membranes of most plant
and all bacterial cells. Cholesterol molecules are oriented with their small hydrophilic
hydroxyl group toward the membrane surface and the remainder of the molecule
embedded in the lipid bilayer. The hydrophobic rings of a cholesterol molecule are
flat and rigid, and they interfere with the movements of the fatty acid tails of the
phospholipids.

Figure 26. The Chemical Structure of Membrane Lipids

(Karp, 2013)

The Nature and Importance of the Lipid Bilayer Each type of cellular membrane
has its own characteristic lipid composition, differing from one another in the types of
lipids, the nature of the head groups, and the particular species of fatty acyl chain(s).
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Because of this structural variability, it is estimated that some biological membranes

contain hundreds of chemically distinct species of phospholipid. The role of this
remarkable diversity of lipid species remains the subject of interest and speculation.
The lipids of a membrane are more than simple structural elements; they can have
important effects on the biological properties of a membrane (Table 1). Lipid
composition can determine the physical state of the membrane and influence the
activity of particular membrane proteins. Membrane lipids also provide the
precursors for highly active chemical messengers that regulate cellular function.
Membranes are never seen to have a free edge; they are always continuous,
unbroken structures. As a result, membranes form extensive interconnected
networks within the cell. Because of the flexibility of the lipid bilayer, membranes are
deformable and their overall shape can change, as occurs during locomotion or cell
division. The lipid bilayer is thought to facilitate the regulated fusion or budding of
membranes. For example, the events of secretion, in which cytoplasmic vesicles
fuse to the plasma membrane, or of fertilization, where two cells fuse to form a single
cell, involve processes in which two separate membranes come together to become
one continuous sheet. Another important feature of the lipid bilayer is its ability to
self-assemble, which can be demonstrated more easily within a test tube than a
living cell. If, for example, a small amount of phosphatidylcholine is dispersed in an
aqueous solution, the phospholipid molecules assemble spontaneously to form the
walls of fluid-filled spherical vesicles, called liposomes. The walls of these
liposomes consist of a continuous lipid bilayer that is organized in the same manner
as that of the lipid bilayer of a natural membrane. Liposomes have proven invaluable
in membrane research. Membrane proteins can be inserted into liposomes and their
function studied in a much simpler environment than that of a natural membrane.
Liposomes have also been developed as vehicles to deliver drugs or DNA molecules
within the body.

Table 1. Lipid Composition of Some Biological Membranes

Membrane Carbohydrates
The plasma membranes of eukaryotic cells also contain carbohydrate. Depending on
the species and cell type, the carbohydrate content of the plasma membrane ranges
between 2 and 10 percent by weight. More than 90 percent of the membrane’s
carbohydrate is covalently linked to proteins to form glycoproteins; the remaining

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carbohydrate is covalently linked to lipids to form glycolipids. All of the carbohydrate

of the plasma membrane faces outward into the extracellular space. The
carbohydrate of internal cellular membranes also faces away from the cytosol.

The addition of carbohydrate, or glycosylation, is the most complex of these

modifications. The carbohydrate of glycoproteins is present as short, branched
hydrophilic oligosaccharides, typically having fewer than about 15 sugars per
chain. In contrast to most high-molecular-weight carbohydrates (such as glycogen,
starch, or cellulose), which are polymers of a single sugar, the oligosaccharides
attached to membrane proteins and lipids can display considerable variability in
composition and structure. Oligosaccharides may be attached to several different
amino acids by two major types of linkages (Figure 27). These carbohydrate
projections play an important role in mediating the interactions of a cell with its
environment and sorting of membrane proteins to different cellular compartments.
The carbohydrates of the glycolipids of the red blood cell plasma membrane
determine whether a person’s blood type is A, B, AB, or O. A person having blood
type A has an enzyme that adds an N-acetylgalactosamine to the end of the chain,
whereas a person with type B blood has an enzyme that adds galactose to the chain
terminus. These two enzymes are encoded by alternate versions of the same gene,
yet they recognize different substrates. People with AB blood type possess both
enzymes, whereas people with O blood type lack enzymes capable of attaching
either terminal sugar. The function of the ABO blood-group antigens remains a
mystery.

Figure 27. Two Types of Linkages that Join Sugars to a Polypeptide Chain
(Karp, 2013)

Structures and Functions of Membrane Proteins

Depending on the cell type and the particular organelle within that cell, a membrane
may contain hundreds of different proteins. Each membrane protein has a defined
orientation relative to the cytoplasm, so that the properties of one surface of a
membrane are very different from those of the other surface. This asymmetry is
referred to as membrane “sidedness.” In the plasma membrane, for example, those
parts of membrane proteins that interact with other cells or with extracellular
substances project outward into the extracellular space, whereas those parts of

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membrane proteins that interact with cytoplasmic molecules project into the cytosol.
Membrane proteins can be grouped into three distinct classes distinguished by the
intimacy of their relationship to the lipid bilayer (Figure 28). These are

1. Integral proteins that penetrate the lipid bilayer. Integral proteins are
transmembrane proteins; that is, they pass entirely through the lipid bilayer and
thus have domains that protrude from both the extracellular and cytoplasmic sides of
the membrane. Some integral proteins have only one membrane-spanning segment,
whereas others are multispanning. Genome-sequencing studies suggest that integral
proteins constitute 20–30 percent of all encoded proteins.

2. Peripheral proteins that are located entirely outside of the lipid bilayer, on either
the cytoplasmic or extracellular side, yet are associated with the surface of the
membrane by noncovalent bonds.

3. Lipid-anchored proteins that are located outside the lipid bilayer, on either the
extracellular or cytoplasmic surface, but are covalently linked to a lipid molecule that
is situated within the bilayer.

Integral Membrane Proteins

Most integral membrane proteins function in the following capacities: as receptors
that bind specific substances at the membrane surface, as channels or transporters
involved in the movement of ions and solutes across the membrane, or as agents
that transfer electrons during the processes of photosynthesis and respiration. Like
the phospholipids of the bilayer, integral membrane proteins are also amphipathic,
having both hydrophilic and hydrophobic portions. The portions of an integral
membrane protein that reside within the lipid bilayer tend to have a hydrophobic
character. Amino acid residues in these transmembrane domains form van der
Waals interactions with the fatty acyl chains of the bilayer, which seals the protein
into the lipid “wall” of the membrane. As a result, the permeability barrier of the
membrane is preserved and the protein is brought into direct contact with
surrounding lipid molecules. Lipid molecules that are closely associated with a
membrane protein can play an important role in the activity of the protein, although
the degree to which a particular protein requires specific interactions with particular
lipid molecules remains unclear. Those portions of an integral membrane protein that
project into either the cytoplasm or extracellular space, these nonembedded
domains tend to have hydrophilic surfaces that interact with water-soluble
substances (lowmolecular- weight substrates, hormones, and other proteins) at the
edge of the membrane. Several large families of membrane proteins contain an
interior channel that provides an aqueous passageway through the lipid bilayer. The
linings of these channels typically contain key hydrophilic residues at strategic
locations. Integral proteins need not be fixed structures but may be able to move
laterally within the membrane.

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Figure 28. Three Classes of Membrane Protein

a. Integral protein, b. Peripheral protein and c. Lipid-anchored protein
(Karp, 2013)

Identifying Transmembrane Domains

A great deal can be learned about the structure of a membrane protein and its
orientation within the lipid bilayer from a computer-based (computational) analysis of
its amino acid sequence, which is readily deduced from the nucleotide sequence of
an isolated gene. The first question one might ask is: Which segments of the
polypeptide chain are actually embedded in the lipid bilayer? Those segments of a
protein embedded within the membrane, which are described as the
transmembrane domains, have a simple structure; they consist of a string of about
20 predominantly nonpolar amino acids that span the core of the lipid bilayer. The
chemical structure of a single transmembrane helix which depicts the two-
dimensional structure of glycophorin A, the major integral protein of the erythrocyte
plasma membrane. Of the 20 amino acids that make up the lone _ helix of a
glycophorin monomer, all but three have hydrophobic side chains (or an H atom in
the case of the glycine residues). The exceptions are serine and threonine, which
are noncharged, polar residues.

Peripheral Membrane Proteins

Peripheral proteins are associated with the membrane by weak electrostatic bonds.
Peripheral proteins can usually be solubilized by extraction with high-concentration
salt solutions that weaken the electrostatic bonds holding peripheral proteins to a
membrane. In actual fact, the distinction between integral and peripheral proteins is
blurred because many integral membrane proteins consist of several polypeptides,
some that penetrate the lipid bilayer and others that remain on the periphery. The
best studied peripheral proteins are located on the internal (cytosolic) surface of the
plasma membrane, where they form a fibrillar network that acts as a membrane

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“skeleton”. These proteins provide mechanical support for the membrane and
function as an anchor for integral membrane proteins. Other peripheral proteins on
the internal plasma membrane surface function as enzymes, specialized coats, or
factors that transmit transmembrane signals. Peripheral proteins typically have a
dynamic relationship with the membrane, being recruited to the membrane or
released from the membrane depending on prevailing conditions.

Lipid-Anchored Membrane Proteins Several types of lipid-anchored membrane

proteins can be distinguished. Numerous proteins present on the external face of the
plasma membrane are bound to the membrane by a small, complex oligosaccharide
linked to a molecule of phosphatidylinositol that is embedded in the outer leaflet of
the lipid bilayer. Peripheral membrane proteins containing this type of glycosyl-
phosphatidylinositol linkage are called GPI-anchored proteins. They were discovered
when it was shown that certain membrane proteins could be released by a
phospholipase that specifically recognized and cleaved inositol-containing
phospholipids. The normal cellular scrapie protein PrPC is a GPI-linked molecule, as
are various receptors, enzymes, and cell-adhesion proteins. A rare type of anemia,
paroxysmal nocturnal hemoglobinuria, results from a deficiency in GPI synthesis that
makes red blood cells susceptible to lysis. Another group of proteins present on the
cytoplasmic side of the plasma membrane is anchored to the membrane by one or
more long hydrocarbon chains embedded in the inner leaflet of the lipid bilayer. At
least two proteins associated with the plasma membrane in this way (Src and Ras)
have been implicated in the transformation of a normal cell to a malignant state.

Activity No. 5.1

NAME_____________PROGRAM and YR. LEVEL____________DATE__________

Cell Membrane & Tonicity Worksheet

Composition of the Cell Membrane & Functions

Fill in the blanks with the appropriate term.

The cell membrane is also called the __________ membrane and is made of
aphospholipid __________. The phospholipids have a hydrophilic (water attracting)
____________and two hydrophobic (water repelling) ________. The head of a
phospholipidis made of an alcohol and ____________group, while the tails are
chains of _____________. Phospholipids can move ____________ laterally but
rarely flip flop from one side to the other. They allow non-polar and other _________
molecules to pass into or outof the cell. These molecules move from an area of
__________concentration to anarea of low concentration. This type of movement or
____________is known assimple __________because it does not require _______.

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Another type of lipid in the cell membrane is _________ that makes the membrane
more fluid. Also embedded in the phospholipid bilayer are _________that also aid in
diffusion and in cell recognition. Water molecules move across the cell membrane
through specialized proteins known as ______________. Proteins called__________
proteins go all the way through the bilayer. Large molecules like
_______/carbohydrates use proteins to help move across cell membranes. Some of
the membrane proteins have carbohydrate ____________attached to help cells in
recognize each other and certain molecules.

List 4 functions of the cell or plasma membrane:

a.
b.
c.
d.

Label the parts of the cell membrane.

MEMBRANE LIPIDS AND MEMBRANE FLUIDITY

The physical state of the lipid of a membrane is described by its fluidity (or viscosity).
Consider a simple artificial bilayer composed of phosphatidylcholine and
phosphatidylethanolamine, whose fatty acids are largely unsaturated. If the
temperature of the bilayer is kept relatively warm, the lipid exists in a relatively fluid
state. At this temperature, the lipid bilayer is best described as a two-dimensional
liquid crystal. As in a crystal, the molecules still retain a specified orientation; in this
case, the long axes of the molecules tend toward a parallel arrangement, yet
individual phospholipids can rotate around their axis or move laterally within the
plane of the bilayer. If the temperature is slowly lowered, a point is reached where
the bilayer distinctly changes. The lipid is converted from a liquid crystalline phase to
a frozen crystalline gel in which the movement of the phospholipid fatty acid chains is
greatly restricted. The temperature at which this change occurs is called the
transition temperature. The transition temperature of a particular bilayer depends
on the ability of the lipid molecules to be packed together, which depends in turn on

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the particular lipids of which it is constructed. Saturated fatty acids have the shape of
a straight, flexible rod. Cis-unsaturated fatty acids, on the other hand, have crooks in
the chain at the sites of a double bond. Consequently, phospholipids with saturated
chains pack together more tightly than those containing unsaturated chains. The
greater the degree of unsaturation of the fatty acids of the bilayer, the lower the
temperature before the bilayer gels. The introduction of one double bond in a
molecule of stearic acid lowers the melting temperature almost 60_C. Another factor
that influences bilayer fluidity is fatty acid chain length. The shorter the fatty acyl
chains of a phospholipid, the lower its melting temperature.

The physical state of the membrane is also affected by cholesterol. Because of their
orientation within the bilayer, cholesterol molecules disrupt the close packing of fatty
acyl chains and interfere with their mobility. The presence of cholesterol tends to
abolish sharp transition temperatures and creates a condition of intermediate fluidity.
In physiologic terms, cholesterol tends to increase the durability while decreasing the
permeability of a membrane.

The Importance of Membrane Fluidity

What effect does the physical state of the lipid bilayer have on the biological
properties of the membrane? Membrane fluidity provides a perfect compromise
between a rigid, ordered structure in which mobility would be absent and a
completely fluid, nonviscous liquid in which the components of the membrane could
not be oriented and structural organization and mechanical support would be lacking.
In addition, fluidity allows for interactions to take place within the membrane. For
example, membrane fluidity makes it possible for clusters of membrane proteins to
assemble at particular sites within the membrane and form specialized structures,
such as intercellular junctions, light-capturing photosynthetic complexes, and
synapses. Because of membrane fluidity, molecules that interact can come together,
carry out the necessary reaction, and move apart. Fluidity also plays a key role in
membrane assembly. Membranes arise only from preexisting membranes, and their
growth is accomplished by the insertion of lipids and proteins into the fluid matrix of
the membranous sheet. Many of the most basic cellular processes, including cell
movement, cell growth, cell division, formation of intercellular junctions, secretion,
and endocytosis, depend on the movement of membrane components and would
probably not be possible if membranes were rigid, nonfluid structures.

Maintaining Membrane Fluidity

The internal temperature of most organisms (birds and mammals) fluctuates with the
temperature of the external environment. Since it is essential for many activities that
the membranes of a cell remain in a fluid state, cells respond to changing conditions
by altering the types of phospholipids of which they are made. Maintenance of
membrane fluidity is an example of homeostasis at the cellular level and can be
demonstrated in various ways. For example, if the temperature of a culture of cells is
lowered, the cells respond metabolically. The initial “emergency” response is
mediated by enzymes that remodel membranes, making the cell more cold resistant.
Remodeling is accomplished by (1) desaturating single bonds in fatty acyl chains to
form double bonds, and (2) reshuffling the chains between different phospholipid
molecules to produce ones that contain two unsaturated fatty acids, which greatly
lowers the melting temperature of the bilayer. Desaturation of single bonds to form
double bonds is catalyzed by enzymes called desaturases. Reshuffling is

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accomplished by phospholipases, which split the fatty acid from the glycerol
backbone, and acyltransferases, which transfer fatty acids between phospholipids. In
addition, the cell changes the types of phospholipids being synthesized in favor of
ones containing more unsaturated fatty acids. As a result of the activities of these
various enzymes, the physical properties of a cell’s membranes are matched to the
prevailing environmental conditions. Maintenance of fluid membranes by
adjustments in fatty acyl composition has been demonstrated in a variety of
organisms, including hibernating mammals, pond-dwelling fish whose body
temperature changes markedly from day to night, cold-resistant plants, and bacteria
living in hot springs.

Lipid Rafts
Every so often an issue emerges that splits the community of cell biologists into
believers and nonbelievers. The issue of lipid rafts falls into this category. When
membrane lipids are extracted from cells and used to prepare artificial lipid bilayers,
cholesterol and sphingolipids tend to self-assemble into microdomains that are more
gelated and highly ordered than surrounding regions consisting primarily of
phosphoglycerides. Because of their distinctive physical properties, such
microdomains tend to float within the more fluid and disordered environment of the
artificial bilayer. As a result, these patches of cholesterol and sphingolipid are
referred to as lipid rafts. When added to these artificial bilayers, certain proteins
tend to become concentrated in the lipid rafts, whereas others tend to remain outside
their boundaries. GPI-anchored proteins show a particular fondness for the ordered
regions of the bilayer. The controversy arises over whether similar types of
cholesterol-rich lipid rafts, exist within living cells. Most of the evidence in favor of
lipid rafts is derived from studies that employ unnatural treatments, such as
detergent extraction or cholesterol depletion, which makes the results difficult to
interpret. Attempts to demonstrate the presence of lipid rafts in living cells have
generally been unsuccessful, which can either mean that such rafts do not exist or
they are so small (5 to 25 nm diameter) and short-lived as to be difficult to detect
with current techniques.

THE DYNAMIC NATURE OF THE PLASMA MEMBRANE

The lipid bilayer can exist in a relatively fluid state. As a result, a phospholipid can
move laterally within the same leaflet with considerable ease. The mobility of
individual lipid molecules within the bilayer of the plasma membrane can be directly
observed under the microscope by linking the polar heads of the lipids to gold
particles or fluorescent compounds. It is estimated that a phospholipid can diffuse
from one end of a bacterium to the other end in a second or two. In contrast, it takes
a phospholipid molecule a matter of hours to days to move across to the other
leaflet. Thus, of all the possible motions that a phospholipid can make, its flipflop to
the other side of the membrane is the most restricted. This finding is not surprising.
For flip-flop to occur, the hydrophilic head group of the lipid must pass through the
internal hydrophobic sheet of the membrane, which is thermodynamically
unfavorable. However, cells contain enzymes that actively move certain
phospholipids from one leaflet to the other. These enzymes play a role in
establishing lipid asymmetry and may also reverse the slow rate of passive
transmembrane movement. Because lipids provide the matrix in which integral
proteins of a membrane are embedded, the physical state of the lipid is an important

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determinant of the mobility of integral proteins. The demonstration that integral

proteins can move within the plane of the membrane was a cornerstone in the
formulation of the fluid-mosaic model. The dynamic properties of membrane proteins
have been revealed in several ways.

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 with a common cytoplasm and a
single, continuous plasma membrane. Cells are induced to fuse with one another by
making the outer surface of the cells “sticky” so that their plasma membranes adhere
to one another. Cells can be induced to fuse by addition of certain inactivated viruses
that attach to the surface membrane, by adding the compound polyethylene glycol,
or by a mild electric shock. Cell fusion has played an important role in cell biology
and is currently used in an invaluable technique to prepare specific antibodies. The
first experiments to demonstrate that membrane proteins could move within the
plane of the membrane utilized cell fusion, and they were reported in 1970 by Larry
Frye and Michael Edidin of Johns Hopkins University. In their experiments, mouse
and human cells were fused, and the locations of specific proteins of the plasma
membrane were followed once the two membranes had become continuous.

Restrictions on Protein and Lipid Mobility

Several techniques allow researchers to follow the movements of molecules in the
membranes of living cells using the light microscope. In a technique called
fluorescence recovery after photobleaching (FRAP), integral membrane
components in cultured cells are first labeled by linkage to a fluorescent dye. A
particular membrane protein can be labeled using a specific probe, such as a
fluorescent antibody. Once labeled, cells are placed under the microscope and
irradiated by a sharply focused laser beam that bleaches the fluorescent molecules
in its path, leaving a circular spot on the surface of the cell that is largely devoid of
fluorescence. If the labeled proteins in the membrane are mobile, then the random
movements of these molecules should produce a gradual reappearance of
fluorescence in the irradiated circle. The rate of fluorescence recovery provides a
direct measure of the rate of diffusion of the mobile molecules. The extent of
fluorescence recovery provides a measure of the percentage of the labeled
molecules that are free to diffuse. Early studies utilizing FRAP suggested that (1)
membrane proteins moved much more slowly in a plasma membrane than they
would in a pure lipid bilayer and (2) a significant fraction of membrane proteins (30 to
70 percent) were not free to diffuse back into the irradiated circle.

Control of Membrane Protein Mobility

It is apparent that plasma membrane proteins are not totally free to drift around
randomly on the lipid “sea,” but instead they are subjected to various influences that
affect their mobility. Some membranes are crowded with proteins, so that the
random movements of one molecule can be impeded by its neighbors . The
strongest influences on an integral membrane protein are thought to be exerted from
just beneath the membrane on its cytoplasmic face. The plasma membranes of
many cells possess a fibrillar network, or “membrane skeleton,” consisting of
peripheral proteins situated on the cytoplasmic surface of the membrane. A certain
proportion of a membrane’s integral protein molecules are either tethered to the
membrane skeleton or otherwise restricted by it. Information concerning the

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presence of membrane barriers has been obtained using an innovative technique

that allows investigators to trap integral proteins and drag them through the plasma
membrane with a known force. This technique, which uses an apparatus referred to
as optical tweezers, takes advantage of the tiny optical forces that are generated by
a focused laser beam. The integral proteins to be studied are tagged with antibody-
coated beads, which serve as handles that can be gripped by the laser beam. It is
generally found that optical tweezers can drag an integral protein for a limited
distance before the protein encounters a barrier that causes it to be released from
the laser’s grip. As it is released, the protein typically springs backward, suggesting
that the barriers are elastic structures. One approach to studying factors that affect
membrane protein mobility is to genetically modify cells so that they produce altered
membrane proteins. Integral proteins whose cytoplasmic portions have been
genetically deleted often move much greater distances than their intact counterparts,
indicating that barriers reside on the cytoplasmic side of the membrane. These
findings suggest that the membrane’s underlying skeleton forms a network of
“fences” around portions of the membrane, creating compartments that restrict the
distance an integral protein can travel. Proteins move across the boundaries from
one compartment to another through breaks in the fences. Such openings are
thought to appear and disappear along with the dynamic disassembly and
reassembly of parts of the meshwork. Membrane compartments may keep specific
combinations of proteins in close enough proximity to facilitate their interaction.
Integral proteins lacking that portion that would normally project into the extracellular
space typically move at a much faster rate than the wild-type version of the protein.
This finding suggests that the movement of a transmembrane protein through the
bilayer is slowed by extracellular materials that can entangle the external portion of
the protein molecule.

The Red Blood Cell: An Example of Plasma Membrane Structure

Of all the diverse types of membranes, the plasma membrane of the human
erythrocyte (red blood cell) is the most studied and best understood. There are
several reasons for the popularity of this membrane. The cells are inexpensive to
obtain and readily available in huge numbers from whole blood. They are already
present as single cells and need not be dissociated from a complex tissue. The cells
are simple by comparison with other cell types, lacking nuclear and cytoplasmic
membranes that inevitably contaminate plasma membrane preparations from other
cells. In addition, purified, intact erythrocyte plasma membranes can be obtained
simply by placing the cells in a dilute (hypotonic) salt solution. The cells respond to
this osmotic shock by taking up water and swelling, a phenomenon termed
hemolysis. As the surface area of each cell increases, the cell becomes leaky, and
the contents, composed almost totally of dissolved hemoglobin, flow out of the cell
leaving behind a plasma membrane “ghost”.

THE MOVEMENT OF SUBSTANCES ACROSS CELL MEMBRANES

Because the contents of a cell are completely surrounded by its plasma membrane,
all communication between the cell and the extracellular medium must be mediated
by this structure. In a sense, the plasma membrane has a dual function. On one
hand, it must retain the dissolved materials of the cell so that they do not simply leak
out into the environment, while on the other hand, it must allow the necessary
exchange of materials into and out of the cell. The lipid bilayer of the membrane is

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ideally suited to prevent the loss of charged and polar solutes from a cell.
Consequently, some special provision must be made to allow the movement of
nutrients, ions, waste products, and other compounds, in and out of the cell. There
are basically two means for the movement of substances through a membrane:
passively by diffusion or actively by an energy-coupled transport process. Both types
of movements lead to the net flux of a particular ion or compound. The term net flux
indicates that the movement of the substance into the cell (influx) and out of the cell
(efflux) is not balanced, but that one exceeds the other. Several different processes
are known by which substances move across membranes: simple diffusion through
the lipid bilayer; simple diffusion through an aqueous, protein-lined channel; diffusion
that is facilitated by a protein transporter; and active transport, which requires an
energy-driven protein “pump” capable of moving substances against a concentration
gradient.
REV
The Energetics of Solute Movement
Diffusion is a spontaneous process in which a substance moves from a region of
high concentration to a region of low concentration, eventually eliminating the
concentration difference between the two regions. Diffusion depends on the random
thermal motion of solutes and is an exergonic process driven by an increase in
entropy. We will restrict the following discussion to diffusion of substances across
membranes. The free-energy change when an uncharged solute (a nonelectrolyte)
diffuses across a membrane depends on the magnitude of the concentration
gradient, that is, the difference in concentration on each side of the membrane.

Diffusion of Substances through Membranes

Two qualifications must be met before a nonelectrolyte can diffuse passively across
a plasma membrane. The substance must be present at higher concentration on one
side of the membrane than the other, and the membrane must be permeable to the
substance. A membrane may be permeable to a given solute either (1) because that
solute can pass directly through the lipid bilayer, or (2) because that solute can
traverse an aqueous pore that spans the membrane.

The Diffusion of Water through Membranes

Water molecules move much more rapidly through a cell membrane than do
dissolved ions or small polar organic solutes, which are essentially nonpenetrating.
Because of this difference in the penetrability of water versus solutes, membranes
are said to be semipermeable. Water moves readily through a semipermeable
membrane from a region of lower solute concentration to a region of higher solute
concentration. This process is called osmosis, and it is readily demonstrated by
placing a cell into a solution containing a nonpenetrating solute at a concentration
different than that present within the cell itself. When two compartments of different
solute concentration are separated by a semipermeable membrane, the
compartment of higher solute concentration is said to be hypertonic (or
hyperosmotic) relative to the compartment of lower solute concentration, which is
described as being hypotonic (or hypoosmotic). When a cell is placed into a
hypotonic solution, the cell rapidly gains water by osmosis and swells. Conversely, a
cell placed into a hypertonic solution rapidly loses water by osmosis and shrinks.
These simple observations show that a cell’s volume is controlled by the difference
between the solute concentration inside the cell and that in the extracellular medium.
The swelling and shrinking of cells in slightly hypotonic and hypertonic media are

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usually only temporary events. Within a few minutes, the cells recover and return to
their original volume. In a hypotonic medium, recovery occurs as the cells lose ions,
thereby reducing their internal osmotic pressure. In a hypertonic medium, recovery
occurs as the cells gain ions from the medium. Once the internal solute
concentration (which includes a high concentration of dissolved proteins) equals the
external solute concentration, the internal and external fluids are isotonic (or
isosmotic), and no net movement of water into or out of the cells occurs. Osmosis is
an important factor in a multitude of bodily functions. Your digestive tract, for
example, secretes several liters of fluid daily, which is reabsorbed osmotically by the
cells that line your intestine. If this fluid weren’t reabsorbed, as happens in cases of
extreme diarrhea, you would face the prospect of rapid dehydration. Plants utilize
osmosis in different ways. Unlike animal cells, which are generally isotonic with the
medium in which they are bathed, plant cells are generally hypertonic compared to
their fluid environment. As a result, there is a tendency for water to enter the cell,
causing it to develop an internal (turgor) pressure that pushes against its surrounding
wall. Turgor pressure provides support for nonwoody plants and for the nonwoody
parts of trees, such as the leaves. If a plant cell is placed into a hypertonic medium,
its volume shrinks as the plasma membrane pulls away from the surrounding cell
wall, a process called plasmolysis. The loss of water due to plasmolysis causes
plants to lose their support and wilt.

The Diffusion of Ions through Membranes

The lipid bilayer that constitutes the core of biological membranes is highly
impermeable to charged substances, including small ions such as Na_, K_, Ca2_,
and Cl_. Yet the rapid movement (conductance) of these ions across membranes
plays a critical role in a multitude of cellular activities, including formation and
propagation of a nerve impulse, secretion of substances into the extracellular space,
muscle contraction, regulation of cell volume, and the opening of stomatal pores on
plant leaves. In 1955, Alan Hodgkin and Richard Keynes of Cambridge University
first proposed that cell membranes contain ion channels, that is, openings in the
membrane that are permeable to specific ions. During the late 1960s and 1970s,
Bertil Hille of the University of Washington and Clay Armstrong of the University of
Pennsylvania began to obtain evidence for the existence of such channels. The final
“proof ” emerged through the work of Bert Sakmann and Erwin Neher at the Max-
Planck Institute in Germany in the late 1970s and early 1980s who developed
techniques to monitor the ionic current passing through a single ion channel.
These landmark studies marked the first successful investigations into the activities
of individual protein molecules. Today, biologists have identified a bewildering variety
of ion channels, each formed by integral membrane proteins that enclose a central
aqueous pore. As might be predicted, mutations in the genes encoding ion channels
can lead to many serious diseases. Most ion channels are highly selective in
allowing only one particular type of ion to pass through the pore. As with the passive
diffusion of other types of solutes across membranes, the diffusion of ions through a
channel is always downhill, that is, from a state of higher energy to a state of lower
energy. Most of the ion channels that have been identified can exist in either an open
or a closed conformation; such channels are said to be gated. The opening and
closing of the gates are subject to complex physiologic regulation and can be
induced by a variety of factors depending on the particular channel. Three major
categories of gated channels are distinguished:

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1. Voltage-gated channels whose conformational state depends on the difference

in ionic charge on the two sides of the membrane.
2. Ligand-gated channels whose conformational state depends on the binding of a
specific molecule (the ligand), which is usually not the solute that passes through the
channel. Some ligand-gated channels are opened (or closed) following the binding of
a molecule to the outer surface of the channel; others are opened (or closed)
following the binding of a ligand to the inner surface of the channel. For example,
neurotransmitters, such as acetylcholine, act on the outer surface of certain cation
channels, while cyclic nucleotides, such as cAMP, act on the inner surface of certain
calcium ion channels.
3. Mechano-gated channels whose conformational state depends on mechanical
forces (e.g., stretch tension) that are applied to the membrane. In 1998, Roderick
MacKinnon and his colleagues at Rockefeller University provided the first atomic-
resolution image of an ion channel protein, in this case, a bacterial K_ion channel
called KcsA.

Facilitated Diffusion
Substances always diffuse across a membrane from a region of higher concentration
on one side to a region of lower concentration on the other side, but they do not
always diffuse through the lipid bilayer or through a channel. In many cases, the
diffusing substance first binds selectively to a membrane-spanning protein, called a
facilitative transporter, that facilitates the diffusion process. The binding of the
solute to the facilitative transporter on one side of the membrane is thought to trigger
a conformational change in the protein, exposing the solute to the other surface of
the membrane, from where it can diffuse down its concentration gradient. Because
they operate passively, that is, without being coupled to an energy-releasing system,
facilitated transporters can mediate the movement of solutes equally well in both
directions. The direction of net flux depends on the relative concentration
of the substance on the two sides of the membrane. Facilitated diffusion, as this
process is called, is similar in many ways to an enzyme-catalyzed reaction. Like
enzymes, facilitative transporters are specific for the molecules they transport,
discriminating, for example, between D and L stereoisomers. In addition, both
enzymes and transporters exhibit saturation-type kinetics. Unlike ion channels, which
can conduct millions of ions per second, most facilitative transporters can move only
hundreds to thousands of solute molecules per second across the membrane.
Another important feature of facilitative transporters is that, like enzymes and ion
channels, their activity can be regulated. Facilitated diffusion is particularly important
in mediating the entry and exit of polar solutes, such as sugars and amino acids, that
do not penetrate the lipid bilayer.

The Glucose Transporter: An Example of Facilitated Diffusion

Glucose is the body’s primary source of direct energy, and most mammalian cells
contain a membrane protein that facilitates the diffusion of glucose from the
bloodstream into the cell. A gradient favoring the continued diffusion of glucose into
the cell is maintained by phosphorylating the sugar after it enters the cytoplasm, thus
lowering the intracellular glucose concentration. Humans have at least five related
proteins (isoforms) that act as facilitative glucose transporters. These isoforms,
termed GLUT1 to GLUT5, are distinguished by the tissues in which they are located,
as well as their kinetic and regulatory characteristics. Insulin is a hormone produced
by endocrine cells of the pancreas and plays a key role in maintaining proper blood

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sugar levels. An increase in blood glucose levels triggers the secretion of insulin,
which stimulates the uptake of glucose into various target cells, most notably skeletal
muscle and fat cells (adipocytes). Insulin-responsive cells share a common isoform
of the facilitative glucose transporter, specifically GLUT4. When insulin levels are
low, these cells contain relatively few glucose transporters on their plasma
membrane. Instead, the transporters are present within the membranes of
cytoplasmic vesicles. Rising insulin levels act on target cells to stimulate the fusion of
the cytoplasmic vesicles to the plasma membrane, which moves transporters to the
cell surface where they can bring glucose into the cell.

Active Transport
Life cannot exist under equilibrium conditions. Nowhere is this more apparent than in
the imbalance of ions across the plasma membrane. There are differences in
concentration of the major ions between the outside and inside of the cell. The ability
of a cell to generate such steep concentration gradients across its plasma
membrane cannot occur by either simple or facilitated diffusion. Rather, these
gradients must be generated by active transport. Like facilitated diffusion, active
transport depends on integral membrane proteins that selectively bind a particular
solute and move it across the membrane in a process driven by changes in the
protein’s conformation. Unlike facilitated diffusion, however, movement of a solute
against a gradient requires the coupled input of energy. Consequently, the
endergonic movement of ions or other solutes across the membrane against a
concentration gradient is coupled to an exergonic process, such as the hydrolysis of
ATP, the absorbance of light, the transport of electrons, or the flow of other
substances down their gradients. Proteins that carry out active transport are often
referred to as “pumps.”

Coupling Active Transport to ATP Hydrolysis

In 1957, Jens Skou, a Danish physiologist, discovered an ATP-hydrolyzing enzyme
in the nerve cells of a crab that was only active in the presence of both Na and K
ions. Skou proposed, and correctly so, that this enzyme, which was responsible for
ATP hydrolysis, was the same protein that was active in transporting the two ions;
the enzyme was called the Na/K-ATPase, or the sodium–potassium pump. Unlike
the protein-mediated movement of a facilitated diffusion system, which will carry the
substance equally well in either direction, active transport drives the movement of
ions in only one direction. It is the Na/K-ATPase that is responsible for the large
excess of Na ions outside of the cell and the large excess of K ions inside the cell.
The positive charges carried by these two cations are balanced by negative charges
carried by various anions so that the extracellular and intracellular compartments
are, for the most part, electrically neutral. Cl ions are present at greater
concentration outside of cells, where they balance the extracellular Na ions. The
abundance of intracellular K ions is balanced primarily by excess negative charges
carried by proteins and nucleic acids. A large number of studies have indicated that
the ratio of NaK pumped by the Na/K-ATPase is not 11, but 32. In other words, for
each ATP hydrolyzed, three sodium ions are pumped out as two potassium ions are
pumped in.

5.2 Pumps, Carriers, Channels

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Although lipid bilayers provide a barrier to diffusion of ions and polar molecules,
protein pores provide selective passages for ions and other larger molecules across
membranes. Integral proteins that control membrane permeability fall into three
broad classes: pumps, carriers and channels, each with distinct properties. These
proteins allow cells to control solute traffic across membranes, as essential feature of
many physiological processes.
A. Pumps are enzymes that utilize energy from Adenosine Triphosphate (ATP), light
or other sources to move ions and other solutes across membranes at relatively
modest rates. They establish concentration gradients between membrane-bound
compartments. Protein pumps transport ions and other solutes across membranes
up concentration gradients as great as 1 million-fold. Energy for this task can come
from a variety of sources: light, oxidation-reduction reactions, or most commonly,
hydrolysis of ATP. Energy is conserved in the form of transmembrane electrical or
chemical gradients of the transported ion or solute. The potential energy in these ion
gradients drives a variety of energy-requiring processes. Most known biological
pumps translocate cations. Although they could just as well move anions, cations
were selected during the evolution of early life forms 3 billion years ago.
Pumps are also called primary active transporters because they transduce
electromagnetic or chemical energy directly into transmembrane concentration
gradients. Some carriers use ion gradients created by pumps to drive the uphill
movement of other ions or solutes, so these are called secondary transporters.
Channels are passive transporters, allowing net diffusion of ions and water only
down their concentration gradients.
Diversity of Membrane Pumps
A vast array of integral membrane proteins can rupture energy from an external
source to pump ions and other solutes across biological membranes. The proteins
families differ in their energy sources and transported materials.
[Link]-Driven Proton Pumping by Bacteriorhodopsin
Owing to its simplicity, its small size, and the availability of a high-resolution
structure, more is known about light-driven transport of protons by bacteriorhodopsin
than about any other pump. This pump allows the halophillic (salt-loving) Archaea
Halobacterium halobium to convert light energy into a proton gradient across its
plasma membrane. Bacteriorhodopsin absorbs light and uses the energy to pump
protons out of the cell. A proton-driven ATP synthase uses this proton gradient to
make ATP.
B. Carriers are enzyme-like proteins that provide passive pathways for solutes to
move across membranes down their concentration gradients from a region of higher
concentration to one of lower concentration. Each conformational change in a carrier
protein translocates a limited number of solutes across the membrane. Carriers use
ion gradients as a source of energy to perform a remarkable variety of work. Some
carriers use translocation of an ion down its concentration gradient to drive another
ion or solute up a concentration gradient.
Carriers are integral membrane proteins that use electrochemical gradients to move
select chemical substances across lipid bilayers. They are also known as

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facilitators or porters. Carriers that transport a single substrate across a membrane

down its concentration gradient are called uniporters. Remarkably, many carriers
also transport substrates up concentration gradients, provided that their passage
through the carrier and across the membrane is coupled to the transport of another
substrate down its electrochemical gradient. Glucose provides good examples of
both downhill and uphill movement through different carriers. The GLUT1 uniporter
allows glucose to move down its concentration gradient from plasma into red blood
cells. On the other hand, the SGLT1 carrier uses a gradient of Na established by
NAK-ATPase pump to move glucose up its concentration gradient into intestinal
cells. It is called symporter, since glucose and Na move in the same direction.
Another class of carriers called antiporters move a substrate in the opposite
direction to the ion gradient driving the reaction.
When a carrier uses an ion gradient to provide the energy to transport a substrate, it
is said to catalyze a secondary reaction. In this sense, pumps catalyze primary
transport reactions, using energy from ATP hydrolysis, electron transport, or
absorption of light to create ion gradients. Coupling an ion gradient created by
pumps to drive transport by a carrier is called a chemiosmotic cycle.
C. Channels are ion-specific pores that typically open and close transiently in a
regulated manner. When a channel is open, a flood of ions passes quickly across the
membrane through the channel, driven by electrical and concentration gradients.
The movement of ions through open channels controls the electrical potential across
membranes, so that changes in channel activity produce rapid electrical signals in
excitable membranes of nerves, muscles, and other cells. Channels are integral
membrane proteins with transmembrane pores that allow particular ions or small
molecules to cross a lipid bilayer.
Activity No. 2
Diffusion, Facilitated Diffusion, Active Transport

Directions:
Fill in the table the differences, similarities and functions of Diffusion, Facilitated
Diffusion, Active Transport

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Self-Check
1.1
Answer substantially:
1. Describe the importance of the plasma membrane to the living
LOOKING BACKprocesses taking place inside the cell.

Review the following concepts:

 Cells are separated from the external world by a thin, fragile structure called
the plasma membrane. Functions include: Compartmentalization, Scaffold
for biochemical activities, Providing a selectively permeable barrier,
Transporting solutes, Responding to external signals, Intercellular interaction,
and Energy transduction.

 Membranes are lipid–protein assemblies in which the components are held

together in a thin sheet by noncovalent bonds. The core of the membrane
consists of a sheet of lipids arranged in a bimolecular layer. The lipid bilayer
serves primarily as a structural backbone of the membrane and provides the
barrier that prevents random movements of water-soluble materials into and
out of the cell. The proteins of the membrane, on the other hand, carry out
most of the specific functions.

 Diffusion is a spontaneous process in which a substance moves from a region

of high concentration to a region of low concentration, eventually eliminating
the concentration difference between the two regions.

 Facilitated Diffusion - the diffusing substance first binds selectively to a

membrane-spanning protein, called a facilitative transporter, that facilitates
the diffusion process. The binding of the solute to the facilitative transporter
on one side of the membrane is thought to trigger a conformational change in
the protein, exposing the solute to the other surface of the membrane, from
where it can diffuse down its concentration gradient.

 Active Transport - depends on integral membrane proteins that selectively

bind a particular solute and move it across the membrane in a process driven
by changes in the protein’s conformation.

Post test

I. Multiple Choice. Encircle the letter of the best answer.

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1. Which of the following is the protein located entirely outside of the lipid bilayer,
on either the cytoplasmic or extracellular side?
e. integral protein c. integrated protein
b. peripheral protein d. glycoprotein

2. Which of the following is not true about the phospholipid molecule?

a. Hydrophobic region c. amphipatic
b. b. hydrophillic region d. all are correct responses

3. Which of the channels whose conformational state depends on mechanical

forces?
a. Voltage-gated channels c. Mechano-gated channels
b. Ligand-gated channel d. Osmosis channels

4. Which statement represents a notable difference between simple diffusion

and facilitated diffusion?
a. Unlike simple diffusion, facilitated diffusion can transport ligands against a
concentrate gradient.
b. Unlike simple diffusion, the rate of facilitated diffusion is limited by the
number of transport proteins in the membrane.
c. Unlike simple diffusion, facilitated diffusion requires energy in the form of
ATP.
d. Unlike simple diffusion, facilitated diffusion can occur in any type of cell.

5. Which of the following is not true about the plasma membrane?

a. protection c. energy
b. transport d. none of the above

6. Which intermolecular process primarily drives the formation of a bilayer when

phospholipids are added to water?

a. Lipids cause water to arrange in an ordered, unfavorable cage-like
structure. Forcing lipids into a bilayer reduces this effect.
b. Phospholipids self-assemble into a bilayer due to the strong affinity they
have for each other.
c. The ordered arrangement of a bilayer is more favorable than the
disordered state of individual free-floating phospholipids.
d. A bilayer arrangement maximizes the strength of Van der Waals forces
among phospholipids.

7. Which statement best describes how cholesterol affects cell membrane

fluidity?
a. Cholesterol increases fluidity at high temperatures and decreases fluidity
at low temperatures.
b. Cholesterol increases fluidity at high temperatures and increases fluidity at
low temperatures.
c. Cholesterol decreases fluidity at high temperatures and decreases fluidity
at low temperatures.

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d. Cholesterol decreases fluidity at high temperatures and increases fluidity

at low temperatures.

8. Compared to a typical animal cell, the cell membranes on the paw of a polar
bear would most likely have an increased concentration of which
macromolecule?
a. Unsaturated phospholipids
b. Saturated phospholipids
c. Aquaporin proteins
d. Potassium channel proteins

9. Which molecule diffuses through a membrane most quickly?

a. Ethylene
b. Urea
c. Glucose
d. Benzene

10. Glucose typically enters the cell through which mechanism?

a. Pinocytosis through a channel protein
b. Active transport by a glucose transport protein
c. Simple diffusion through the cell membrane
d. Facilitated diffusion through a carrier protein

References

Karp, G. Karp, G.( 2013) Cell and Molecular Biology, Wiley and Sons

Pollard, T.D. and Earnshaw, W.C. 2008. Cell Biology. Saunders Elsevier, USA

Raven, J. 2018. Biology. McGraw Hill. USA.

[Link]

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Bio 3 – Cell and Molecular Biology 28