Chapter 5 Biological membranes and transports

Introduction
Each cell of your body is encased in a tiny bubble of membrane. This membrane has
about the consistency of...salad oil. The first time I read that factoid, I didn't find it
very reassuring! Salad oil seems like an awfully fragile boundary to place between a
cell and the rest of the world. Luckily, the plasma membrane turns out to be very
well-suited to its job, salad oil texture and all.

What exactly is its job? The plasma membrane not only defines the borders of the cell,
but also allows the cell to interact with its environment in a controlled way. Cells
must be able to exclude, take in, and excrete various substances, all in specific
amounts. In addition, they must able to communicate with other cells, identifying
themselves and sharing information.

To perform these roles, the plasma membrane needs lipids, which make a semi-
permeable barrier between the cell and its environment. It also needs proteins, which
are involved in cross-membrane transport and cell communication, and
carbohydrates (sugars and sugar chains), which decorate both the proteins and lipids
and help cells recognize each other.

Here, we’ll take a closer look at the different components of the plasma membrane,
examining their roles, their diversity, and how they work together to make a flexible,
sensitive, and secure boundary around the cell.

Fluid mosaic model

The currently accepted model for the structure of the plasma membrane, called
the fluid mosaic model, was first proposed in 1972. This model has evolved over
time, but it still provides a good basic description of the structure and behaviour of
membranes in many cells.
According to the fluid mosaic model, the plasma membrane is a mosaic of
components—primarily, phospholipids, cholesterol, and proteins—that move freely
and fluidly in the plane of the membrane. In other words, a diagram of the membrane
(like the one below) is just a snapshot of a dynamic process in which phospholipids
and proteins are continually sliding past one another.
Interestingly enough, this fluidity means that if you insert a very fine needle into a
cell, the membrane will simply part to flow around the needle; once the needle is
removed, the membrane will flow back together seamlessly.
The principal components of the plasma membrane are lipids (phospholipids and
cholesterol), proteins, and carbohydrate groups that are attached to some of the lipids
and proteins.
 A phospholipid is a lipid made of glycerol, two fatty acid tails, and a
phosphate-linked head group. Biological membranes usually involve two layers
of phospholipids with their tails pointing inward, an arrangement called
a phospholipid bilayer.
 Cholesterol, another lipid composed of four fused carbon rings, is found
alongside phospholipids in the core of the membrane.
 Membrane proteins may extend partway into the plasma membrane, cross the
membrane entirely, or be loosely attached to its inside or outside face.
 Carbohydrate groups are present only on the outer surface of the plasma
membrane and are attached to proteins, forming glycoproteins, or lipids,
forming glycolipids.
The proportions of proteins, lipids, and carbohydrates in the plasma membrane vary
between different types of cells. For a typical human cell, however, proteins account
for about 50 percent of the composition by mass, lipids (of all types) account for about
40 percent, and the remaining 10 percent comes from carbohydrates.

Phospholipids
Phospholipids, arranged in a bilayer, make up the basic fabric of the plasma
membrane. They are well-suited for this role because they are amphipathic, meaning
that they have both hydrophilic and hydrophobic regions.
The hydrophilic, or “water-loving,” portion of a phospholipid is its head, which
contains a negatively charged phosphate group as well as an additional small group
(of varying identity, “R” in the diagram at left), which may also or be charged or polar.
The hydrophilic heads of phospholipids in a membrane bilayer face outward,
contacting the aqueous (watery) fluid both inside and outside the cell. Since water is a
polar molecule, it readily forms electrostatic (charge-based) interactions with the
phospholipid heads.

The hydrophobic, or “water-fearing,” part of a phospholipid consists of its long,

nonpolar fatty acid tails. The fatty acid tails can easily interact with other nonpolar
molecules, but they interact poorly with water. Because of this, it’s more energetically
favourable for the phospholipids to tuck their fatty acid tails away in the interior of
the membrane, where they are shielded from the surrounding water. The
phospholipid bilayer formed by these interactions makes a good barrier between the
interior and exterior of the cell, because water and other polar or charged substances
cannot easily cross the hydrophobic core of the membrane.
[Can water cross the plasma membrane at all?]
Thanks to their amphipathic nature, phospholipids aren’t just well-suited to form a
membrane bilayer. Instead, this is something they’ll do spontaneously under the right
conditions! In water or aqueous solution, phospholipids tend to arrange themselves
with their hydrophobic tails facing each other and their hydrophilic heads facing out.
If the phospholipids have small tails, they may form a micelle (a small, single-layered
sphere), while if they have bulkier tails, they may form a liposome (a hollow droplet of
bilayer membrane).

Proteins
Proteins are the second major component of plasma membranes. There are two main
categories of membrane proteins: integral and peripheral.
Integral membrane proteins are, as their name suggests, integrated into the
membrane: they have at least one hydrophobic region that anchors them to the
hydrophobic core of the phospholipid bilayer. Some stick only partway into the
membrane, while others stretch from one side of the membrane to the other and are
exposed on either side. Proteins that extend all the way across the membrane are
called transmembrane proteins.

The portions of an integral membrane protein found inside the membrane are
hydrophobic, while those that are exposed to the cytoplasm or extracellular fluid
tend to be hydrophilic. Transmembrane proteins may cross the membrane just once,
or may have as many as twelve different membrane-spanning sections. A typical
membrane-spanning segment consists of 20-25 hydrophobic amino acids arranged in
an alpha helix, although not all transmembrane proteins fit this model. Some integral
membrane proteins form a channel that allows ions or other small molecules to pass,
as shown below.

Peripheral membrane proteins are found on the outside and inside surfaces of
membranes, attached either to integral proteins or to phospholipids. Unlike integral
membrane proteins, peripheral membrane proteins do not stick into the hydrophobic
core of the membrane, and they tend to be more loosely attached.

Carbohydrates
Carbohydrates are the third major component of plasma membranes. In general, they
are found on the outside surface of cells and are bound either to proteins
(forming glycoproteins) or to lipids (forming glycolipids). These carbohydrate chains
may consist of 2-60 monosaccharide units and can be either straight or branched.
Along with membrane proteins, these carbohydrates form distinctive cellular markers,
sort of like molecular ID badges, that allow cells to recognize each other. These
markers are very important in the immune system, allowing immune cells to
differentiate between body cells, which they shouldn’t attack, and foreign cells or
tissues, which they should.

Membrane fluidity
The structure of the fatty acid tails of the phospholipids is important in determining
the properties of the membrane, and in particular, how fluid it is.

Saturated fatty acids have no double bonds (are saturated with hydrogens), so they
are relatively straight. Unsaturated fatty acids, on the other hand, contain one or
more double bonds, often resulting in a bend or kink. (You can see an example of a
bent, unsaturated tail in the diagram of phospholipid structure that appears earlier in
this article.) The saturated and unsaturated fatty acid tails of phospholipids behave
differently as temperature drops:

 At cooler temperatures, the straight tails of saturated fatty acids can pack
tightly together, making a dense and fairly rigid membrane.

 Phospholipids with unsaturated fatty acid tails cannot pack together as tightly
because of the bent structure of the tails. Because of this, a membrane
containing unsaturated phospholipids will stay fluid at lower temperatures
than a membrane made of saturated ones.

Most cell membranes contain a mixture of phospholipids, some with two saturated
(straight) tails and others with one saturated and one unsaturated (bent) tail. Many
organisms—fish are one example—can adjust physiologically to cold environments by
changing the proportion of unsaturated fatty acids in their membranes. For more
information about saturated and unsaturated fatty acids, see the article on lipids.

In addition to phospholipids, animals have an additional membrane component that

helps to maintain fluidity. Cholesterol, another type of lipid that is embedded among
the phospholipids of the membrane, helps to minimize the effects of temperature on
fluidity.
At low temperatures, cholesterol increases fluidity by keeping phospholipids from
packing tightly together, while at high temperatures, it actually reduces
fluidity^{3,4}3,4start superscript, 3, comma, 4, end superscript. In this way,
cholesterol expands the range of temperatures at which a membrane maintains a
functional, healthy fluidity.

The components of the plasma membrane

Component Location

Phospholipids Main fabric of the membrane

Tucked between the hydrophobic tails of the membrane

Cholesterol phospholipids

Embedded in the phospholipid bilayer; may or may not extend

Integral proteins through both layers

Peripheral On the inner or outer surface of the phospholipid bilayer, but not
proteins embedded in its hydrophobic core

Attached to proteins or lipids on the extracellular side of the

Carbohydrates membrane (forming glycoproteins and glycolipids)
 Osmosis and tonicity
Introduction
Have you ever forgotten to water a plant for a few days, then come back to find your
once-perky arugula a wilted mess? If so, you already know that water balance is very
important for plants. When a plant wilts, it does so because water moves out of its
cells, causing them to lose the internal pressure—called turgor pressure—that
normally supports the plant.

Why does water leave the cells? The amount of water outside the cells drops as the
plant loses water, but the same quantity of ions and other particles remains in the
space outside the cells. This increase in solute, or dissolved particle, concentration
pulls the water out of the cells and into the extracellular spaces in a process known
as osmosis.

Formally, osmosis is the net movement of water across a semipermeable membrane

from an area of lower solute concentration to an area of higher solute concentration.
This may sound odd at first, since we usually talk about the diffusion of solutes that
are dissolved in water, not about the movement of water itself. However, osmosis is
important in many biological processes, and it often takes place at the same time that
solutes diffuse or are transported. Here, we’ll look in more detail at how osmosis
works, as well as the role it plays in the water balance of cells.

How it works
Why does water move from areas where solutes are less concentrated to areas where
they are more concentrated?

This is actually a complicated question. To answer it, let’s take a step back and
refresh our memory on why diffusion happens. In diffusion, molecules move from a
region of higher concentration to one of lower concentration—not because they’re
aware of their surroundings, but simply as a result of probabilities. When a substance
is in gas or liquid form, its molecules will be in constant, random motion, bouncing or
sliding around one another. If there are lots of molecules of a substance in
compartment A and no molecules of that substance in compartment B, it’s very
unlikely—impossible, actually—that a molecule will randomly move from B to A. On
the other hand, it’s extremely likely that a molecule will move from A to B. You can
picture all of those molecules bouncing around in compartment A and some of them
making the leap over to compartment B. So, the net movement of molecules will be
from A to B, and this will be the case until the concentrations become equal.
In the case of osmosis, you can once again think of molecules—this time, water
molecules—in two compartments separated by a membrane. If neither compartment
contains any solute, the water molecules will be equally likely to move in either
direction between the compartments. But if we add solute to one compartment, it will
affect the likelihood of water molecules moving out of that compartment and into the
other—specifically, it will reduce this likelihood.

Why should that be? There are some different explanations out there. The one that
seems to have the best scientific support involves the solute molecules actually
bouncing off the membrane and physically knocking the water molecules backwards
and away from it, making them less likely to cross.

Regardless of the exact mechanisms involved, the key point is that the more solute
water contains, the less apt it will be to move across a membrane into an adjacent
compartment. This results in the net flow of water from regions of lower solute
concentration to regions of higher solute concentration.

This process is illustrated in the beaker example above, where there will be a net flow
of water from the compartment on the left to the compartment on the right until the
solute concentrations are nearly balanced. Note that they will not become perfectly
equal in this case because the hydrostatic pressure exerted by the rising water
column on the right will oppose the osmotic driving force, creating an equilibrium that
stops short of equal concentrations.
Tonicity
The ability of an extracellular solution to make water move into or out of a cell by
osmosis is known as its tonicity. A solution's tonicity is related to its osmolarity,
which is the total concentration of all solutes in the solution. A solution with low
osmolarity has fewer solute particles per litre of solution, while a solution with high
osmolarity has more solute particles per litre of solution. When solutions of different
osmolarities are separated by a membrane permeable to water, but not to solute,
water will move from the side with lower osmolarity to the side with higher osmolarity.

Three terms—hypotonic, isotonic, and hypertonic—are used to compare the

osmolarity of a cell to the osmolarity of the extracellular fluid around it.

Note: When we use these terms, we are considering only solutes that cannot cross the
membrane.

 If the extracellular fluid has lower osmolarity than the fluid inside the cell, it’s
said to be hypotonic—hypo means less than—to the cell, and the net flow of
water will be into the cell.

 In the reverse case, if the extracellular fluid has a higher osmolarity than the
cell’s cytoplasm, it’s said to be hypertonic—hyper means greater than—to the
cell, and water will move out of the cell to the region of higher solute
concentration.

 In an isotonic solution—iso means the same—the extracellular fluid has the

same osmolarity as the cell, and there will be no net movement of water into or
out of the cell.

Hypotonic, hypertonic, and isotonic are relative terms. That is, they describe how one
solution compares to another in terms of osmolarity. For instance, if the fluid inside a
cell has a higher osmolarity, concentration of solute, than the surrounding fluid, the
cell interior is hypertonic to the surrounding fluid, and the surrounding fluid
is hypotonic to the cell interior.

Tonicity in living systems

If a cell is placed in a hypertonic solution, water will leave the cell, and the cell will
shrink. In an isotonic environment, the relative concentrations of solute and water are
equal on both sides of the membrane. There is no net water movement, so there is no
change in the size of the cell. When a cell is placed in a hypotonic environment, water
will enter the cell, and the cell will swell.
In the case of a red blood cell, isotonic conditions are ideal, and your body
has homeostatic (stability-maintaining) systems to ensure these conditions stay
constant. If placed in a hypotonic solution, a red blood cell will bloat up and may
explode, while in a hypertonic solution, it will shrivel—making the cytoplasm dense
and its contents concentrated—and may die.

In the case of a plant cell, however, a hypotonic extracellular solution is actually ideal.
The plasma membrane can only expand to the limit of the rigid cell wall, so the cell
won't burst, or lyse. In fact, the cytoplasm in plants is generally a bit hypertonic to
the cellular environment, and water will enter a cell until its internal pressure—
turgor pressure—prevents further influx.

Maintaining this balance of water and solutes is very important to the health of the
plant. If a plant is not watered, the extracellular fluid will become isotonic or
hypertonic, causing water to leave the plant's cells. This results in a loss of turgor
pressure, which you have likely seen as wilting. Under hypertonic conditions, the cell
membrane may actually detach from the wall and constrict the cytoplasm, a state
called plasmolysis (left panel below).
Tonicity is a concern for all living things, particularly those that lack rigid cell walls
and live in hyper- or hypotonic environments. For example, paramecia—pictured
below—and amoebas, which are protists that lack cell walls, may have specialized
structures called contractile vacuoles. A contractile vacuole collects excess water from
the cell and pumps it out, keeping the cell from lysing as it takes on water from its
hypotonic environment.

Diffusion and passive transport

Introduction
Have you been through airport security lately? If you have, you’ve probably noticed
that it’s carefully designed to let some things in (such as passengers with tickets) and
to keep others out (such as weapons, explosives, and bottled water). Flight
attendants, captains, and airport personnel travel through quickly via a special
channel, while regular passengers pass through more slowly, sometimes with a long
wait in line.

In many ways, airport security is a lot like the plasma membrane of a cell. Cell
membranes are selectively permeable, regulating which substances can pass
through, as well as how much of each substance can enter or exit at a given time.
Selective permeability is essential to cells’ ability to obtain nutrients, eliminate
wastes, and maintain a stable interior environment different than that of the
surroundings (maintain homeostasis).

The simplest forms of transport across a membrane are passive. Passive

transport does not require the cell to expend any energy and involves a substance
diffusing down its concentration gradient across a membrane. A concentration
gradient is a just a region of space over which the concentration of a substance
changes, and substances will naturally move down their gradients, from an area of
higher to an area of lower concentration.
In cells, some molecules can move down their concentration gradients by crossing the
lipid portion of the membrane directly, while others must pass through membrane
proteins in a process called facilitated diffusion. Here, we’ll look in more detail at
membrane permeability and different modes of passive transport.

Selective permeability
The phospholipids of plasma membranes are amphipathic: they have both
hydrophilic (water-loving) and hydrophobic (water-fearing) regions. The hydrophobic
core of the plasma membrane helps some materials move through the membrane,
while it blocks the movement of others.

Polar and charged molecules have much more trouble crossing the membrane. Polar
molecules can easily interact with the outer face of the membrane, where the
negatively charged head groups are found, but they have difficulty passing through its
hydrophobic core. Water molecules, for instance, cannot cross the membrane rapidly
(although thanks to their small size and lack of a full charge, they can cross at a slow
rate).

Additionally, while small ions are the right size to slip through the membrane, their
charge prevents them from doing so. This means that ions like sodium, potassium,
calcium, and chloride cannot cross membranes to any significant degree by simple
diffusion, and must instead be transported by specialized proteins (which we’ll
discuss later). Larger charged and polar molecules, like sugars and amino acids, also
need help from proteins to efficiently cross the membrane.
Diffusion
In the process of diffusion, a substance tends to move from an area of high
concentration to an area of low concentration until its concentration becomes equal
throughout a space. For example, think about someone opening a bottle of cleaning
ammonia in the middle of a room. The ammonia molecules will initially be most
concentrated right where the person opened the bottle, with few or no molecules at
the edges of the room. Gradually, the ammonia molecules will diffuse, or spread, away
from the place where they were released, and eventually you’ll be able to smell
ammonia at the edges of the room. Ultimately, if the bottle is capped and the room is
closed, the ammonia molecules will become evenly distributed throughout its volume.

The same will happen with molecules of any type: as a population, they tend to move
from an area where they’re more concentrated to an area where they’re less
concentrated. To understand this, imagine that there’s an area where molecules are
more concentrated (such as where ammonia has just been opened) and an area where
they’re less concentrated (the surrounding room). Since there are lots of ammonia
molecules in the concentrated area, it’s pretty likely that one will move from there into
the non-concentrated area. But since there are few molecules of ammonia in the non-
concentrated area, it’s pretty unlikely that the reverse will happen.

Thus, over time, the net movement of molecules will be out of the more concentrated
area and into the less concentrated one, until the concentrations become equal (at
which point, it’s equally likely for a molecule to move in either direction). This process
does not require any energy input; in fact, a concentration gradient itself is a form of
stored (potential) energy, and this energy is used up as the concentrations equalize.

Molecules can move through the cell’s cytosol by diffusion, and some molecules also
diffuse across the plasma membrane (as shown in the picture above). Each individual
substance in a solution or space has its own concentration gradient, independent of
the concentration gradients of other materials, and will diffuse according to that
gradient. Other factors being equal, a stronger concentration gradient (larger
concentration difference between regions) results in faster diffusion. Thus, in a single
cell, there can be different rates and directions of diffusion for different molecules. For
example, oxygen might move into the cell by diffusion, while at the same time, carbon
dioxide might move out in obedience to its own concentration gradient.

Facilitated diffusion
Some molecules, such as carbon dioxide and oxygen, can diffuse across the plasma
membrane directly, but others need help to cross its hydrophobic core. In facilitated
diffusion, molecules diffuse across the plasma membrane with assistance from
membrane proteins, such as channels and carriers.

A concentration gradient exists for these molecules, so they have the potential to
diffuse into (or out of) the cell by moving down it. However, because they are charged
or polar, they can't cross the phospholipid part of the membrane without help.
Facilitated transport proteins shield these molecules from the hydrophobic core of the
membrane, providing a route by which they can cross. Two major classes of facilitated
transport proteins are channels and carrier proteins.

Channels
Channel proteins span the membrane and make hydrophilic tunnels across it,
allowing their target molecules to pass through by diffusion. Channels are very
selective and will accept only one type of molecule (or a few closely related molecules)
for transport. Passage through a channel protein allows polar and charged
compounds to avoid the hydrophobic core of the plasma membrane, which would
otherwise slow or block their entry into the cell.
Aquaporins are channel proteins that allow water to cross the membrane very
quickly, and they play important roles in plant cells, red blood cells, and certain parts
of the kidney (where they minimize the amount of water lost as urine).

Some channel proteins are open all the time, but others are “gated,” meaning that the
channel can open or close in response to a particular signal (like an electrical signal
or the binding of a molecule). Cells involved in the transmission of electrical signals,
such as nerve and muscle cells, have gated ion channels for sodium, potassium, and
calcium ions in their membranes. The opening and closing of these channels, and the
resulting shifts in ion levels inside the cell, play an important role in electrical
transmission along membranes (in nerve cells) and in muscle contraction (in muscle
cells).

Carrier proteins
Another class of transmembrane proteins involved in facilitated transport consists of
the carrier proteins. Carrier proteins can change their shape to move a target
molecule from one side of the membrane to the other.

Diagram showing how a carrier protein can bind a target molecule on one side of the
membrane, undergo a shape change, and release the target molecule on the other
side of the membrane.

Like channel proteins, carrier proteins are typically selective for one or a few
substances. Often, they will change shape in response to binding of their target
molecule, with the shape change moving the molecule to the opposite side of the
membrane. The carrier proteins involved in facilitated diffusion simply provide
hydrophilic molecules with a way to move down an existing concentration gradient
(rather than acting as pumps).
Channel and carrier proteins transport material at different rates. In general, channel
proteins transport molecules much more quickly than do carrier proteins. This is
because channel proteins are simple tunnels; unlike carrier proteins, they don’t need
to change shape and “reset” each time they move a molecule. A typical channel
protein might facilitate diffusion at a rate of tens of millions of molecules per second,
whereas a carrier protein might work at a rate of a thousand or so molecules per
second.

Active transport
Introduction
Passive transport is a great strategy for moving molecules into or out of a cell. It's
cheap, it's easy, and all the cell has to do is sit there and let the molecules diffuse in.
But...it also doesn't work in every situation. For instance, suppose the sugar glucose
is more concentrated inside of a cell than outside. If the cell needs more sugar in to
meet its metabolic needs, how can it get that sugar in?

Here, the cell can't import glucose for free using diffusion, because the natural
tendency of the glucose will be to diffuse out rather than flowing in. Instead, the cell
must bring in more glucose molecules via active transport. In active transport,
unlike passive transport, the cell expends energy (for example, in the form of ATP) to
move a substance against its concentration gradient.

Here, we’ll look in more detail at gradients of molecules that exist across cell
membranes, how they can help or hinder transport, and how active transport
mechanisms allow molecules to move against their gradients.

Electrochemical gradients
We have already discussed simple concentration gradients, in which a substance is
found in different concentrations over a region of space or on opposite sides of a
membrane. However, because atoms and molecules can form ions and carry positive
or negative electrical charges, there may also be an electrical gradient, or difference in
charge, across a plasma membrane. In fact, living cells typically have what’s called
a membrane potential, an electrical potential difference (voltage) across their cell
membrane.
An electrical potential difference exists whenever there is a net separation of charges
in space. In the case of a cell, positive and negative charges are separated by the
barrier of the cell membrane, with the inside of the cell having extra negative charges
relative to the outside. The membrane potential of a typical cell is -40 to -80 millivolts,
with the minus sign meaning that inside of the cell is more negative than the outside.
The cell actively maintains this membrane potential, and we’ll see how it forms in the
section on the sodium-potassium pump (below).

As an example of how the membrane potential can affect ion movement, let’s look at
sodium and potassium ions. In general, the inside of a cell has a higher
concentration of potassium (K+) and a lower concentration of sodium (Na+) than
the extracellular fluid around it.

 If sodium ions are outside of a cell, they will tend to move into the cell based on
both their concentration gradient (the lower concentration of Na+ in the cell)
and the voltage across the membrane (the more negative charge on the inside
of the membrane).

 Because K+ is positive, the voltage across the membrane will encourage its
movement into the cell, but its concentration gradient will tend to drive it out of
 the cell (towards the region of lower concentration). The final concentrations of
potassium on the two sides of the membrane will be a balance between these
opposing forces.

The combination of concentration gradient and voltage that affects an ion’s movement
is called the electrochemical gradient.

Active transport: moving against a gradient

To move substances against a concentration or electrochemical gradient, a cell must
use energy. Active transport mechanisms do just this, expending energy (often in the
form of ATP) to maintain the right concentrations of ions and molecules in living cells.
In fact, cells spend much of the energy they harvest in metabolism to keep their active
transport processes running. For instance, most of a red blood cell’s energy is used to
maintain internal sodium and potassium levels that differ from those of the
surrounding environment.

Active transport mechanisms can be divided into two categories. Primary active
transport directly uses a source of chemical energy (e.g., ATP) to move molecules
across a membrane against their gradient. Secondary active transport (co-
transport), on the other hand, uses an electrochemical gradient – generated by active
transport – as an energy source to move molecules against their gradient, and thus
does not directly require a chemical source of energy such as ATP. We’ll look at each
type of active transport in greater detail below.

Primary active transport

One of the most important pumps in animal cells is the sodium-potassium pump,
which moves Na+ out of cells, and K+ into them. Because the transport process uses
ATP as an energy source, it is considered an example of primary active transport.

Not only does the sodium-potassium pump maintain correct concentrations of

Na+ and K+ in living cells, but it also plays a major role in generating the voltage
across the cell membrane in animal cells. Pumps like this, which are involved in the
establishment and maintenance of membrane voltages, are known as electrogenic
pumps. The primary electrogenic pump in plants is one that pumps hydrogen ions
(H+) rather than sodium and potassium.
The sodium-potassium pump cycle

The sodium-potassium pump transports sodium out of and potassium into the cell in
a repeating cycle of conformational (shape) changes. In each cycle, three sodium ions
exit the cell, while two potassium ions enter. This process takes place in the following
steps:

1. To begin, the pump is open to the inside of the cell. In this form, the pump
really likes to bind (has a high affinity for) sodium ions, and will take up three
of them.

2. When the sodium ions bind, they trigger the pump to hydrolyze (break down)
ATP. One phosphate group from ATP is attached to the pump, which is then
said to be phosphorylated. ADP is released as a by-product.

3. Phosphorylation makes the pump change shape, re-orienting itself so it opens

towards the extracellular space. In this conformation, the pump no longer likes
to bind to sodium ions (has a low affinity for them), so the three sodium ions
are released outside the cell.

4. In its outward-facing form, the pump switches allegiances and now really likes
to bind to (has a high affinity for) potassium ions. It will bind two of them, and
this triggers removal of the phosphate group attached to the pump in step 2.

5. With the phosphate group gone, the pump will change back to its original form,
opening towards the interior of the cell.
 6. In its inward-facing shape, the pump loses its interest in (has a low affinity for)
potassium ions, so the two potassium ions will be released into the cytoplasm.
The pump is now back to where it was in step 1, and the cycle can begin again.

This may seem like a complicated cycle, but it just involves the protein going back
and forth between two forms: an inward-facing form with high affinity for sodium (and
low affinity for potassium) and an outward-facing form with high affinity for
potassium (and low affinity for sodium). The protein can be toggled back and forth
between these forms by the addition or removal of a phosphate group, which is in
turn controlled by the binding of the ions to be transported.

How the sodium-potassium pump generates a membrane potential

How, exactly, does the sodium-potassium pump establish a voltage across the
membrane? It’s tempting to simply make an argument based on stoichiometry: for
every three ions of sodium that move out, only two ions of potassium move in,
resulting in a more negative cell interior. While this charge ratio does make the cell’s
interior slightly more negative, it actually accounts for only a tiny fraction of the
sodium-potassium pump’s effect on membrane potential.

Instead, the sodium-potassium pump acts primarily by building up a high

concentration of potassium ions inside the cell, which makes potassium’s
concentration gradient very steep. The gradient is steep enough that potassium ions
will move out of the cell (via channels), despite a growing negative charge on the
interior. This process continues until the voltage across the membrane is large
enough to counterbalance potassium’s concentration gradient. At this balance point,
the inside of the membrane is negative relative to the outside. This voltage will be
maintained as long as K+ concentration in the cell stays high, but will disappear if
K+ stops being imported.

For more explanation of how the voltage across the membrane is established, take a
look at the membrane potential article in the neurobiology section.

Secondary active transport

The electrochemical gradients set up by primary active transport store energy, which
can be released as the ions move back down their gradients. Secondary active
transport uses the energy stored in these gradients to move other substances against
their own gradients.
As an example, let's suppose we have a high concentration of sodium ions in the
extracellular space (thanks to the hard work of the sodium-potassium pump). If a
route such as a channel or carrier protein is open, sodium ions will move down their
concentration gradient and return to the interior of the cell.

In secondary active transport, the movement of the sodium ions down their gradient
is coupled to the uphill transport of other substances by a shared carrier protein
(a co-transporter). For instance, in the figure below, a carrier protein lets sodium
ions move down their gradient, but simultaneously brings a glucose molecule up its
gradient and into the cell. The carrier protein uses the energy of the sodium gradient
to drive the transport of glucose molecules.

In secondary active transport, the two molecules being transported may move either
in the same direction (i.e., both into the cell), or in opposite directions (i.e., one into
and one out of the cell). When they move in the same direction, the protein that
transports them is called a symporter, while if they move in opposite directions, the
protein is called an antiporter.
 Bulk transport
Introduction
Imagine you are a macrophage: a merciless white blood cell that stalks, amoeba-like,
through the tissues of the body, looking for pathogens, dead and dying cells, and
other undesirables. When you encounter one of these, your task is not just to destroy
it, but to devour it whole. (Chomp!)

This complete annihilation may seem a bit over the top, but it serves two useful
purposes. First, it recovers valuable macromolecules for the body’s use. Second, in
the case of foreign pathogens, it allows the macrophage to present fragments of the
pathogen on its surface. This display alerts other immune cells that the pathogen is
present and triggers an immune response.

Let’s take a step back, though. How does a macrophage “eat” a pathogen or a piece of
cellular debris? In the past few sections, we’ve talked about ways that ions and small
molecules, such as sugars and amino acids, can enter and exit the cell via channels
and transporters. Channels and carrier proteins are great for letting specific small
molecules cross the membrane, but they are too small (and too picky about what they
transport) to let a cell take up something like an entire bacterium.

Instead, cells need bulk transport mechanisms, in which large particles (or large
quantities of smaller particles) are moved across the cell membrane. These
mechanisms involve enclosing the substances to be transported in their own small
globes of membrane, which can then bud from or fuse with the membrane to move
the substance across. For instance, a macrophage engulfs its pathogen dinner by
extending membrane "arms" around it and enclosing it in a sphere of membrane
called a food vacuole (where it is later digested).

Macrophages provide a dramatic example of bulk transport, and the majority of cells
in your body don’t engulf whole microorganisms. However, most cells do have bulk
transport mechanisms of some kind. These mechanisms allow cells to obtain
nutrients from the environment, selectively “grab” certain particles out of the
extracellular fluid, or release signaling molecules to communicate with neighbours.
Like the active transport processes that move ions and small molecules via carrier
proteins, bulk transport is an energy-requiring (and, in fact, energy-intensive)
process.

Here, we’ll look at the different modes of bulk transport: phagocytosis, pinocytosis,
receptor-mediated endocytosis, and exocytosis.
Endocytosis
Endocytosis (endo = internal, cytosis = transport mechanism) is a general term for
the various types of active transport that move particles into a cell by enclosing them
in a vesicle made out of plasma membrane.

There are variations of endocytosis, but all follow the same basic process. First, the
plasma membrane of the cell invaginates (folds inward), forming a pocket around the
target particle or particles. The pocket then pinches off with the help of specialized
proteins, leaving the particle trapped in a newly created vesicle or vacuole inside the
cell.

Endocytosis can be further subdivided into the following categories: phagocytosis,

pinocytosis, and receptor-mediated endocytosis.

Phagocytosis
Phagocytosis (literally, “cell eating”) is a form of endocytosis in which large particles,
such as cells or cellular debris, are transported into the cell. We’ve already seen one
example of phagocytosis, because this is the type of endocytosis used by the
macrophage in the article opener to engulf a pathogen.
Single-celled eukaryotes called amoebas also use phagocytosis to hunt and consume
their prey. Or at least, they try to – the image series below shows a frustrated amoeba
trying to phagocytose a yeast cell that’s just a tiny bit too big.

Once a cell has successfully engulfed a target particle, the pocket containing the
particle will pinch off from the membrane, forming a membrane-bound compartment
called a food vacuole. The food vacuole will later fuse with an organelle called
a lysosome, the "recycling center" of the cell. Lysosomes have enzymes that break the
engulfed particle down into its basic components (such as amino acids and sugars),
which can then be used by the cell.

Pinocytosis
Pinocytosis (literally, “cell drinking”) is a form of endocytosis in which a cell takes in
small amounts of extracellular fluid. Pinocytosis occurs in many cell types and takes
place continuously, with the cell sampling and re-sampling the surrounding fluid to
get whatever nutrients and other molecules happen to be present. Pinocytosed
material is held in small vesicles, much smaller than the large food vacuole produced
by phagocytosis.
Receptor-mediated endocytosis
Receptor-mediated endocytosis is a form of endocytosis in which receptor proteins
on the cell surface are used to capture a specific target molecule. The receptors,
which are transmembrane proteins, cluster in regions of the plasma membrane
known as coated pits. This name comes from a layer of proteins, called coat proteins,
which are found on the cytoplasmic side of the pit. Clathrin, shown in the diagram
above, is the best-studied coat protein.

When the receptors bind to their specific target molecule, endocytosis is triggered,
and the receptors and their attached molecules are taken into the cell in a vesicle. The
coat proteins participate in this process by giving the vesicle its rounded shape and
helping it bud off from the membrane. Receptor-mediated endocytosis allows cells to
take up large amounts of molecules that are relatively rare (present in low
concentrations) in the extracellular fluid.

Although receptor-mediated endocytosis is intended to bring useful substances into

the cell, other, less friendly particles may gain entry by the same route. Flu viruses,
diphtheria, and cholera toxin all use receptor-mediated endocytosis pathways to gain
entry into cells.

Suppose a certain type of molecule were removed from the blood by receptor-mediated
endocytosis. What would happen if the receptor protein for that molecule were missing
or defective?

Exocytosis
Cells must take in certain molecules, such as nutrients, but they also need to release
other molecules, such as signaling proteins and waste products, to the outside
environment. Exocytosis (exo = external, cytosis = transport mechanism) is a form of
bulk transport in which materials are transported from the inside to the outside of the
cell in membrane-bound vesicles that fuse with the plasma membrane.

Some of these vesicles come from the Golgi apparatus and contain proteins made
specifically by the cell for release outside, such as signaling molecules. Other vesicles
contain wastes that the cell needs to dispose of, such as the leftovers that remain
after a phagocytosed particle has been digested.

These vesicles are transported to the edge of the cell, where they can fuse with the
plasma membrane and release their contents into the extracellular space. Some
vesicles fuse completely with the membrane and are incorporated into it, while others
follow the “kiss-and-run” model, fusing just enough to release their contents
(“kissing” the membrane) before pinching off again and returning to the cell interior.