ANATOMY AND PHYSIOLOGY
CELLULAR FORMS AND FUNCTIONS
LEARN THROUGH YOUR COURSE AND FORTIFY ALL YOUR WEAKNESS WITH MEDICAL KNOWLEDGE
All organisms, from the simplest to the most complex, are composed of cells—whether the single cell of a bacterium or the
trillions of cells that constitute the human body. These cells are
responsible for all structural and functional properties of a living
organism. Cytology,1 the study of cell structure and function, is
therefore indispensable to any true understanding of the workings
of the human body, the mechanisms of disease, and the rationale
of therapy. Thus, this chapter and the next one introduce the basic
cell biology of the human body, and subsequent chapters expand
upon this information as we examine the specialized cellular functions of specific organs.
Concepts of Cellular Structure
Objectives
When you have completed this section, you should be able to
• discuss the development and modern tenets of the cell theory;
• be able to describe cell shapes from their descriptive terms;
• state how big human cells are and discuss factors that limit
cell size;
• discuss the way that developments in microscopy have
changed our view of cell structure; and
• outline the major components of a cell.
Development of the Cell Theory
As you may recall from chapter 1, Robert Hooke had
observed only the empty cell walls of cork when he first
named the cell in 1663. Later, he studied thin slices of fresh
wood and saw cells “filled with juices”—a fluid later
named protoplasm.2 Two centuries later, Theodor
Schwann studied a wide range of animal tissues and concluded that all animals are made of cells. Schwann and
other biologists originally believed that cells came from
nonliving body fluid that somehow congealed and
acquired a membrane and nucleus. This idea of spontaneous generation—that living things arise from nonliving
matter—was rooted in the scientific thought of the times.
For centuries, it was considered simple common sense that
decaying meat turns into maggots, stored grain into
rodents, and mud into frogs. Schwann and his contemporaries merely extended this idea to cells. The idea of spontaneous generation wasn’t discredited until some classic
experiments by French microbiologist Louis Pasteur in
1859. By the end of the nineteenth century, it was established beyond all reasonable doubt that cells arise only
from other cells. The development of biochemistry from
the late nineteenth to the twentieth century made it further
apparent that all physiological processes of the body are based on cellular activity and that the cells of all species
exhibit remarkable biochemical unity. Thus emerged the
generalizations that constitute the modern cell theory:
1. All organisms are composed of cells and cell
products.
2. The cell is the simplest structural and functional
unit of life. There are no smaller subdivisions of a
cell or organism that, in themselves, are alive.
3. An organism’s structure and all of its functions are
ultimately due to the activities of its cells.
4. Cells come only from preexisting cells, not from
nonliving matter. All life, therefore, traces its
ancestry to the same original cells.
5. Because of this common ancestry, the cells of all
species have many fundamental similarities in their
chemical composition and metabolic mechanisms.
Cell Shapes and Sizes
There are about 200 types of cells in the human body, and
they vary greatly in shape (fig. 3.1). Squamous3 (SQUAYmus) cells are thin, flat, and often have angular contours
when viewed from above. Such cells line the esophagus
and cover the skin. Polygonal4 cells have irregularly angular shapes with four, five, or more sides. Some nerve cells
have multiple extensions that give them a starlike, or stellate,5 shape. Cuboidal6 cells are squarish and approximately as tall as they are wide; liver cells are a good example. Columnar cells, such as those lining the intestines,
are markedly taller than wide. Egg cells and fat cells are
spheroid to ovoid (round to oval). Red blood cells are discoid (disc-shaped). Smooth muscle cells are fusiform7
(FEW-zih-form)—thick in the middle and tapered toward
the ends. Skeletal muscle cells are described as fibrous
because of their threadlike shape.
Most human cells range from 10 to 15 micrometers
(m) in diameter. (See the inside back book cover for
units of measurement.) The human egg cell, an exceptionally large 100 m in diameter, is barely visible to the
naked eye. The longest human cells are nerve cells
(sometimes over a meter long) and muscle cells (up to 30
cm long), but both are too slender to be seen with the
naked eye.
There is a limit to how large a cell can be, partly due
to the relationship between its volume and surface area.
The surface area of a cell is proportional to the square of
its diameter, while volume is proportional to the cube of
its diameter. Thus, for a given increase in diameter, cell
volume increases much faster than surface area. Picture a
cuboidal cell 10 m on each side (fig. 3.2). It would have
a surface area of 600 m2 (10 m 10 m 6 sides) and
a volume of 1,000 m3 (10 10 10 m). Now, suppose
it grew by another 10 m on each side. Its new surface area
would be 20 m 20 m 6 2,400 m2
, and its volume would be 20 20 20 m 8,000 m3
. The 20 m
cell has eight times as much protoplasm needing nourishment and waste removal, but only four times as much
membrane surface through which wastes and nutrients
can be exchanged. A cell that is too big cannot support
itself.Think About It
Can you conceive of some other reasons for an
organ to consist of many small cells rather than
fewer larger ones?
General Cell Structure
In Schwann’s time, little was known about cells except
that they were enclosed in a membrane and contained a
nucleus. The fluid between the nucleus and surface membrane, called cytoplasm, was thought to be little more
than a gelatinous mixture of chemicals. The transmission electron microscope (TEM), invented in the mid-twentieth century, radically changed this concept. Using a beam
of electrons in place of light, the TEM enabled biologists
to see a cell’s ultrastructure (fig. 3.3), a fine degree of
detail extending even to the molecular level. The most
important thing about a good microscope is not magnification but resolution—the ability to reveal detail. Any
image can be photographed and enlarged as much as we
wish, but if enlargement fails to reveal any more useful
detail, it is empty magnification. A big fuzzy image is not
nearly as informative as one that is small and sharp. The
TEM reveals far more detail than the light microscope
(LM), even at the same magnification (fig. 3.4). A later invention, the scanning electron microscope (SEM), produces dramatic three-dimensional images at high magnification and resolution (see fig. 3.12), but can only view
surface features.
Table 3.1 gives the sizes of some cells and subcellular objects relative to the resolution of the naked eye,
light microscope, and electron microscope. You can see
why the very existence of cells was unsuspected until the
light microscope was invented and why little was known
about their internal components until the TEM became
available.
Figure 3.5 shows some major constituents of a typical cell. The cell is surrounded by a plasma (cell) membrane made of proteins and lipids. The composition and
functions of this membrane can differ significantly from
one region of a cell to another, especially between the
basal, lateral, and apical (upper) surfaces of cells like the
one pictured.
The cytoplasm is crowded with fibers, tubules, passageways, and compartments (see photographs on pp. 93
and 985). It includes several kinds of organelles and a
supportive framework called the cytoskeleton—all of which
we will study in this chapter. A cell may have 10 billion
protein molecules, including potent enzymes with the
potential to destroy the cell if they are not contained and
isolated from other cellular components. You can imagine
the enormous problem of keeping track of all this material,
directing molecules to the correct destinations, and maintaining order against the incessant trend toward disorder.
Cells maintain order partly by compartmentalizing their
contents in the organelles. The organelles and cytoskeleton are embedded in a clear gel called the cytosol or intracellular fluid (ICF). The fluid outside the cell is extracellular fluid (ECF)
The Cell Surface
Objectives
When you have completed this section, you should be able to
• describe the structure of a plasma membrane;
• explain the functions of the lipid, protein, and carbohydrate
components of the plasma membrane;
• describe a second-messenger system and discuss its importance
in human physiology;
• describe the composition and functions of the glycocalyx
that coats cell surfaces; and
• describe the structure and functions of microvilli, cilia, and
flagella.
Throughout this book, you will find that many of the most
physiologically important processes occur at the surface
of a cell—such events as immune responses, the binding
of egg and sperm, cell-to-cell signaling by hormones, and
the detection of tastes and smells, for example. A subne before we venture into the interior of the cell.
The Plasma Membrane
The electron microscope reveals that the cell and many of
the organelles within it are bordered by a unit membrane,
which appears as a pair of dark parallel lines with a total
thickness of about 7.5 nm (fig. 3.6a). The plasma membrane is the unit membrane at the cell surface. It defines
the boundaries of the cell, governs its interactions with
other cells, and controls the passage of materials into and
out of the cell. The side that faces the cytoplasm is the
intracellular face of the membrane, and the side that faces
outward is the extracellular face.
Membrane Lipids
Figure 3.6b shows our current concept of the molecular
structure of the plasma membrane—an oily film of lipids
with diverse proteins embedded in it. Typically about
98% of the molecules in the membrane are lipids, and
about 75% of the lipids are phospholipids. These
amphiphilic molecules arrange themselves into a bilayer,
with their hydrophilic phosphate-containing heads facing
the water on each side of the membrane and their
hydrophobic tails directed toward the center of the membrane, avoiding the water. The phospholipids drift laterally from place to place, spin on their axes, and flex their
tails. These movements keep the membrane fluid.
Think About It
What would happen if the plasma membrane were
made primarily of a hydrophilic substance such as
carbohydrate? Which of the major themes at the end
of chapter 1 does this point best exemplify?
Cholesterol molecules, found amid the fatty acid
tails, constitute about 20% of the membrane lipids. By
interacting with the phospholipids and “holding them
still,” cholesterol can stiffen the membrane (make it less
fluid) in spots. Higher concentrations of cholesterol, however, can increase membrane fluidity by preventing the
phospholipids from becoming packed closely together.
The remaining 5% of the membrane lipids are glycolipids—phospholipids with short carbohydrate chains
on the extracellular face of the membrane. They help to
form the glycocalyx, a carbohydrate coating on the cell
surface with multiple functions, described shortly.
Membrane Proteins
Although proteins are only about 2% of the molecules of
the plasma membrane, they are larger than lipids and
constitute about 50% of the membrane weight. Some of
them, called integral (transmembrane) proteins, pass
through the membrane. They have hydrophilic regions
in contact with the cytoplasm and extracellular fluid,
and hydrophobic regions that pass back and forth
through the lipid of the membrane (fig. 3.7). Most integral proteins are glycoproteins, which are conjugated
with oligosaccharides on the extracellular side of the
membrane. Many of the integral proteins drift about
freely in the phospholipid film, like ice cubes floating in
a bowl of water. Others are anchored to the cytoskeleton—an intracellular system of tubules and filaments
discussed later. Peripheral proteins do not protrude into
the phospholipid layer but adhere to the intracellular
face of the membrane. A peripheral protein is typically
associated with an integral protein and tethered to the
cytoskeleton.The functions of membrane proteins include the
following:
• Receptors (fig. 3.8a).
The chemical signals by which
cells communicate with each other (epinephrine, for
example) often cannot enter the target cell, but bind to
surface proteins called receptors. Receptors are
usually specific for one particular messenger, much
like an enzyme that is specific for one substrate.
• Second-messenger systems.
When a messenger binds to
a surface receptor, it may trigger changes within the cell
that produce a second messenger in the cytoplasm. This
process involves both transmembrane proteins (the
receptors) and peripheral proteins. Second-messenger
systems are discussed shortly in more detail.
• Enzymes (fig. 3.8b).
Enzymes in the plasma membranes
of cells carry out the final stages of starch and protein
digestion in the small intestine, help produce second
messengers, and break down hormones and other
signaling molecules whose job is done, thus stopping
them from excessively stimulating a cell.
• Channel proteins (fig. 3.8c).
Channel proteins are
integral proteins with pores that allow passage of
water and hydrophilic solutes through the membrane.
Some channels are always open, while others are gates
that open and close under different circumstances,
thus determining when solutes can pass through
(fig. 3.8d). These gates open or close in response to
three types of stimuli: ligand-regulated gates respond
to chemical messengers, voltage-regulated gates to
changes in electrical potential (voltage) across the
plasma membrane, and mechanically regulated gates
to physical stress on a cell, such as stretch and pressure. By controlling the movement of electrolytes
through the plasma membrane, gated channels play an
important role in the timing of nerve signals and
muscle contraction (see insight 3.1).
• Carriers (see figs. 3.18 and 3.19).
Carriers are integral
proteins that bind to glucose, electrolytes, and other
solutes and transfer them to the other side of the
membrane. Some carriers, called pumps, consume
ATP in the process.
• Molecular motors (fig. 3.8e).
These proteins produce
movement by changing shape and pulling on other
molecules. They move materials within a cell, as in
transporting molecules and organelles to their
destinations; they enable some cells, such as white
blood cells, to crawl around in the body’s tissues; and
they make cells change shape, as when a cell
surrounds and engulfs foreign particles or when it
divides in two. Such processes depend on the action
of fibrous proteins, especially actin and myosin, that
pull on the integral proteins of the plasma membrane.
• Cell-identity markers
(fig. 3.8f ). Glycoproteins
contribute to the glycocalyx, a carbohydrate surface
coating discussed shortly. Among other functions, this
acts like an “identification tag” that enables our bodies
to tell which cells belong to it and which are foreign
invaders
.• Cell-adhesion molecules (fig. 3.8g)
. Cells adhere to one
another and to extracellular material through certain
membrane proteins called cell-adhesion molecules
(CAMs). With few exceptions (such as blood cells and
metastasizing cancer cells), cells do not grow or survive
normally unless they are mechanically linked to the
extracellular material. Special events such as sperm-egg
binding and the binding of an immune cell to a cancer
cell also require CAMs.
Insight 3.1 Clinical Application
Calcium Channel Blockers
The walls of the arteries contain smooth muscle that contracts or relaxes
to change their diameter. These changes modify the blood flow and
strongly influence blood pressure. Blood pressure rises when the arteries
constrict and falls when they relax and dilate. Excessive, widespread vasoconstriction can cause hypertension (high blood pressure), and vasoconstriction in the coronary blood vessels of the heart can cause pain (angina)
due to inadequate blood flow to the cardiac muscle. In order to contract,
a smooth muscle cell must open calcium channels in its plasma membrane
and allow calcium to enter from the extracellular fluid. Drugs called calcium channel blockers prevent calcium channels from opening. Thus they
help to relax the arteries, relieve angina, and lower blood pressure.
Second Messengers
Second messengers are of such importance that they
require a closer look. You will find this information essential for your later understanding of hormone and neurotransmitter action. Let’s consider how the hormone epinephrine stimulates a cell. Epinephrine, the “first
messenger,” cannot pass through plasma membranes, so it
binds to a surface receptor. The receptor is linked on the
intracellular side to a peripheral protein called a G protein
(fig. 3.9). G proteins are named for the ATP-like chemical,guanosine triphosphate (GTP), from which they get their
energy. When activated by the receptor, a G protein relays
the signal to another membrane protein, adenylate cyclase
(ah-DEN-ih-late SY-clase). Adenylate cyclase removes two
phosphate groups from ATP and converts it to cyclic AMP
(cAMP), the second messenger. Cyclic AMP then activates
enzymes called kinases (KY-nace-es) in the cytosol.
Kinases add phosphate groups to other cellular enzymes.
This activates some enzymes and deactivates others, but
either way, it triggers a great variety of physiological
changes within the cell.
G proteins play such an enormous range of roles in
physiology and disease that Martin Rodbell and Alfred
Gilman received a 1994 Nobel Prize for discovering them.
Up to 60% of currently used drugs work by altering the
activity of G proteins.
The Glycocalyx
External to the plasma membrane, all animal cells have
a fuzzy coat called the glycocalyx8 (GLY-co-CAY-licks)
(fig. 3.10), which consists of the carbohydrate moieties of the membrane glycolipids and glycoproteins. It is
chemically unique in everyone but identical twins, and
acts like an identification tag that enables the body to
distinguish its own healthy cells from transplanted tissues, invading organisms, and diseased cells. Human
blood types and transfusion compatibility are determined by glycoproteins. The glycocalyx includes the
cell-adhesion molecules that enable cells to adhere to
each other and guide the movement of cells in embryonic development. The functions of the glycocalyx are
summarized in table 3.2.
Microvilli, Cilia, and Flagella
Many cells have surface extensions called microvilli, cilia,
and flagella. These aid in absorption, movement, and sensory processes.
Microvilli
Microvilli9 (MY-cro-VIL-eye; singular, microvillus) are
extensions of the plasma membrane that serve primarily to
increase a cell’s surface area (figs. 3.10 and 3.11a-b). They
are best developed in cells specialized for absorption,
such as the epithelial cells of the intestines and kidney
tubules. They give such cells 15 to 40 times as much
absorptive surface area as they would have if their apical
surfaces were flat. On many cells, microvilli are little more
than tiny bumps on the plasma membrane. On cells of the taste buds and inner ear, they are well developed but serve
sensory rather than absorptive functions.
Individual microvilli cannot be distinguished very
well with the light microscope because they are only 1 to
2 m long. On some cells, they are very dense and appear
as a fringe called the brush border at the apical cell surface. With the scanning electron microscope, they resemble a deep-pile carpet. With the transmission electron
microscope, microvilli typically look like finger-shaped
projections of the cell surface. They show little internal
structure, but some have a bundle of stiff filaments of a
protein called actin. Actin filaments attach to the inside of
the plasma membrane at the tip of the microvillus, and at
its base they extend a little way into the cell and anchor
the microvillus to a protein mesh called the terminal web.
When tugged by another protein in the cytoplasm, actin
can shorten a microvillus to “milk” its absorbed contents
downward into the cell.
Cilia
Cilia (SIL-ee-uh; singular, cilium10) (figs. 3.11c-e and 3.12)
are hairlike processes about 7 to 10 m long. Nearly
every human cell has a single, nonmotile primary cilium
a few micrometers long. Its function in many cases is still
a mystery, but some of them are sensory. In the inner ear,
they play a role in the sense of balance; in the retina of
the eye, they are highly elaborate and form the lightabsorbing part of the receptor cells; and they are thought
to monitor fluid flow through the kidney tubules. In
some cases they open calcium gates in the plasma membrane. Sensory cells in the nose have multiple nonmotile
cilia which bind odor molecules.
Motile cilia are less widespread, occurring mainly
in the respiratory tract and the uterine (fallopian) tubes.
There may be 50 to 200 of these cilia on the surface of
one cell. Cilia beat in waves that sweep across the surface
of an epithelium, always in the same direction (fig. 3.13).
Each cilium bends stiffly forward and produces a power
stroke that pushes along the mucus or other matter.
Shortly after a cilium begins its power stroke, the one just
ahead of it begins, and the next and the next—collectively producing a wavelike motion. After a cilium completes its power stroke, it is pulled limply back by a
recovery stroke that restores it to the upright position,
ready to flex again
.
Think About It
How would the movement of mucus in the
respiratory tract be affected if cilia were equally
stiff on both their power and recovery strokes? Cilia could not beat freely if they were embedded in
sticky mucus (see insight 3.2). Instead, they beat within a
saline (saltwater) layer at the cell surface. Chloride pumps
in the apical plasma membrane produce this layer by
pumping Cl into the extracellular fluid. Sodium ions follow by electrical attraction and water follows by osmosis.
Mucus essentially floats on the surface of this layer and is
pushed along by the tips of the cilia
.Insight 3.2 Clinical Application
Cystic Fibrosis
The significance of chloride pumps becomes especially evident in cystic
fibrosis (CF), a hereditary disease especially affecting white children of
European descent. CF is usually caused by a defect in which cells make
chloride pumps but fail to install them in the plasma membrane. Consequently, there is an inadequate saline layer on the cell surface and the
mucus is dehydrated and overly sticky. This thick mucus plugs the ducts
of the pancreas and prevents it from secreting digestive enzymes into
the small intestine, so digestion and nutrition are compromised. In the
respiratory tract, the mucus clogs the cilia and prevents them from
beating freely. The respiratory tract becomes congested with thick
mucus, often leading to chronic infection and pulmonary collapse. The
mean life expectancy of people with CF is about 30 years.
The structural basis for ciliary movement is a core
called the axoneme11 (ACK-so-neem), which consists of an
array of thin protein cylinders called microtubules. There
are two central microtubules surrounded by a ring of nine
microtubule pairs—an arrangement called the 9 2 structure (see fig. 3.11d). The central microtubules stop at the
cell surface, but the peripheral microtubules continue a
short distance into the cell as part of a basal body that
anchors the cilium. In each pair of peripheral microtubules, one tubule has two little dynein (DINE-een) arms.
Dynein,12 a motor protein, uses energy from ATP to
“crawl” up the adjacent pair of microtubules. When microtubules on the front of the cilium crawl up the microtubules behind them, the cilium bends toward the front.
Flagella
A flagellum13 (fla-JEL-um) is a whiplike structure much
longer than a cilium, but with an identical axoneme. The only
functional flagellum in humans is the tail of a sperm cell.
Membrane Transport
Objectives
When you have completed this section, you should be able to
• explain what is meant by a selectively permeable membrane;
• describe the various mechanisms for transporting material
through the plasma membrane; and
• define osmolarity and tonicity and explain their importance.
The plasma membrane is both a barrier and gateway
between the cytoplasm and extracellular fluid (ECF). It is
selectively permeable—it allows some things through,
such as nutrients and wastes, but usually prevents other
things, such as proteins and phosphates, from entering or
leaving the cell.
The methods of moving substances into or out of a
cell can be classified in two overlapping ways: as passive
or active mechanisms and as carrier-mediated or not. Passive mechanisms require no energy (ATP) expenditure by
the cell. In most cases, the random molecular motion of
the particles themselves provides the energy. Passive
mechanisms include filtration and diffusion (including a
special case of diffusion, osmosis). Active mechanisms,
however, require the cell to consume ATP. These include
active transport and vesicular transport. Carrier-mediated
mechanisms use a membrane protein to transport substances from one side of the membrane to the other. We
will first consider the mechanisms that are not carriermediated (filtration and simple diffusion) and then the
carrier-mediated mechanisms (facilitated diffusion and
active transport).
Filtration
Filtration is a process in which particles are driven
through a selectively permeable membrane by hydrostatic
pressure, the force exerted on a membrane by water. A coffee filter provides an everyday example. The weight of the
water drives water and dissolved matter through the filter,
while the filter holds back larger particles (the coffee
grounds). In physiology, the most important case of filtration is seen in the blood capillaries, where blood pressure
forces fluid through gaps in the capillary wall. This is how
water, salts, nutrients, and other solutes are transferred
from the bloodstream to the tissue fluid and how the kidneys filter wastes from the blood. Capillaries hold back
larger particles such as blood cells and proteins.
Simple Diffusion
Simple diffusion is the net movement of particles from a
place of high concentration to a place of lower concentration as a result of their constant, spontaneous motion. It
can be observed by dropping a dye crystal in a dish of still
water. As the crystal dissolves, it forms a colored zone in
the water that gets larger and larger with time (fig. 3.14).
The dye molecules exhibit net movement from the point
of origin, where their concentration is high, toward the
edges of the dish, where their concentration is low. When
the concentration of a substance differs from one point to
another, we say that it exhibits a concentration gradient.
Particle movement from a region of high concentration
toward a region of lower concentration is said to go down,
or with, the gradient, and movement in the other direction
is said to go up, or against, the gradient.
Diffusion occurs readily in air or water, and has no
need of a membrane. However, if there is a membrane in
the path of the diffusing molecules, and if it is permeable
to that substance, the molecules will pass from one side of the membrane to the other. This is how oxygen passes
from the air we inhale into the bloodstream. Dialysis treatment for kidney disease patients is based on diffusion of
solutes through artificial dialysis membranes.
Diffusion rates are very important to cell survival
because they determine how quickly a cell can acquire
nutrients or rid itself of wastes. Some factors that affect the
rate of diffusion through a membrane are as follows:
• Temperature. Diffusion is driven by the kinetic energy
of the particles, and temperature is a measure of that
kinetic energy. The warmer a substance is, the more
rapidly its particles diffuse. This is why sugar diffuses
more quickly through hot tea than through iced tea.
• Molecular weight. Heavy molecules such as proteins
move more sluggishly and diffuse more slowly than
light particles such as electrolytes and gases. Small
molecules also pass through membrane pores more
easily than large ones.
• “Steepness” of the concentration gradient. The
steepness of a gradient refers to the concentration
difference between two points. Particles diffuse more
rapidly if there is a greater concentration difference
between two points. For example, we can increase
the rate of oxygen diffusion into a patient’s blood by
using an oxygen mask, thus increasing the difference
in oxygen concentration between the air and blood.
• Membrane surface area. As noted earlier, the apical
surface of cells specialized for absorption (for example,
in the small intestine) is often extensively folded into
microvilli. This makes more membrane available for
particles to diffuse through.
• Membrane permeability. Diffusion through a membrane
depends on how permeable it is to the particles. For
example, potassium ions diffuse more rapidly than
sodium ions through a plasma membrane. Nonpolar,
hydrophobic, lipid-soluble substances such as oxygen,
nitric oxide, alcohol, and steroids diffuse through the
phospholipid regions of a plasma membrane. Water and
small charged, hydrophilic solutes such as electrolytes
do not mix with lipids, but diffuse primarily through
channel proteins in the membrane. Cells can adjust their
permeability to such a substance by adding channel
proteins to the membrane or taking them away. Kidney
tubules, for example, do this as a way of controlling the
amount of water eliminated from the body.
Osmosis
Osmosis14 (oz-MO-sis) is the diffusion of water through a
selectively permeable membrane, from the “more watery”
to the “less watery” side. Cells exchange a tremendous
amount of water by osmosis. For example, red blood CELLS pass 100 times their own volume in water through the
plasma membrane every second. Water moves through
plasma membranes by way of channel proteins, especially
those called aquaporins. Cells can regulate the rate of
osmosis by adding aquaporins to the plasma membrane or
removing them. Certain cells of the kidneys, for example,
install or take away aquaporins to regulate the rate of
water loss from the body in the urine.
It is important to note that a solution with a high
solute concentration has a low water concentration, and
vice versa, since solutes take up some of the space that
would otherwise be occupied by water molecules. Therefore, the direction of osmosis will be from a more dilute
solution (where there is more water) to a more concentrated one (where there is less water). In figure 3.15a, for
example, we see a chamber divided by a selectively permeable membrane. Side A contains a solution of large particles that cannot pass through the membrane pores—a
nonpermeating solute such as albumen (egg white protein). Side B contains distilled water. Since albumen takes
up some of the space on side A, water is more concentrated in B than in A, and it diffuses down its concentration gradient from B to A (fig. 3.15b). This is because more
water molecules encounter the membrane per second on
side B than they do on side A, where water is less abundant, and many of those that encounter the membrane
pass through it.
Under these conditions, the water level on side B
would fall and the level on side A would rise. It might
seem as if this would go on indefinitely until side B dried
up. This would not happen, however, because as water
accumulated on side A, it would become heavier and exert
more hydrostatic pressure on that side of the membrane.
This would cause some filtration of water from side A
back to B. At some point, the rate of filtration would equal
the rate of osmosis, water would pass through the membrane equally in both directions, and net osmosis would
slow down and stop. At this point, an equilibrium (balance between opposing forces) would exist. The hydrostatic pressure on side A that would stop osmosis is called
osmotic pressure. The more solute there is on side A, the
greater its osmotic pressure will be.
Think About It
If the albumen concentration on side A were half
what it was in the original experiment, would the
fluid on that side reach a higher or lower level than
before? Explain.
The equilibrium between osmosis and filtration
will be an important consideration as we study fluid
exchange through blood capillaries in chapter 20. Blood
plasma also contains albumins. In the preceding discussion, side A is analogous to the bloodstream and side B
is analogous to the tissue fluid surrounding the capillaries (although tissue fluid is not distilled water). Water leaves the capillaries by filtration, but this is approximately balanced by water moving back into the capillaries by osmosis.
Osmolarity and Tonicity
The osmotic concentration of body fluids has such a great
effect on cellular function that it is important to understand the units in which it is measured. One osmole is 1
mole of dissolved particles. If a solute does not ionize in
water, then 1 mole of the solute yields 1 osmole (osm) of
dissolved particles. A solution of 1 molar (1 M) glucose, for
example, is also 1 osm/L. If a solute does ionize, it yields
two or more dissolved particles in solution. A 1 M solution
of NaCl, for example, contains 1 mole of sodium ions and
1 mole of chloride ions per liter. Both ions affect osmosis
and must be separately counted in a measure of osmotic
concentration. Thus, 1 M NaCl 2 osm/L. Calcium chloride (CaCl2) would yield three ions if it dissociated completely (one Ca2 and two Cl), so 1 M CaCl2 3 osm/L.
Osmolality is the number of osmoles of solute per
kilogram of water, and osmolarity is the number of
osmoles per liter of solution. Most clinical calculations are
based on osmolarity, since it is easier to measure the volume of a solution than the weight of water it contains. At
the concentrations of human body fluids, there is less than
1% difference between osmolality and osmolarity, and the
two terms are nearly interchangeable. All body fluids and
many clinical solutions are mixtures of many chemicals.
The osmolarity of such a solution is the total osmotic concentration of all of its dissolved particles.
A concentration of 1 osm/L is substantially higher than
we find in most body fluids, so physiological concentrations
are usually expressed in terms of milliosmoles per liter
(mOsm/L) (1 mOsm/L 103 osm/L). Blood plasma, tissue
fluid, and intracellular fluid measure about 300 mOsm/L.
Tonicity is the ability of a solution to affect the fluid
volume and pressure in a cell. If a solute cannot pass
through a plasma membrane, but remains more concentrated on one side of the membrane than on the other, it
causes osmosis. A hypotonic15 solution has a lower concentration of nonpermeating solutes than the intracellular
fluid (ICF). Cells in a hypotonic solution absorb water,
swell, and may burst (lyse) (fig. 3.16a). Distilled water is
the extreme example; given to a person intravenously, it
would lyse the blood cells. A hypertonic16 solution is one
with a higher concentration of nonpermeating solutes
than the ICF. It causes cells to lose water and shrivel (crenate) (fig. 3.16c). Such cells may die of torn membranes
and cytoplasmic loss. In isotonic17 solutions, the total concentration of nonpermeating solutes is the same as in the
ICF—hence, isotonic solutions cause no change in cell
volume or shape (fig. 3.16b).
It is essential for cells to be in a state of osmotic equilibrium with the fluid around them, and this requires that
the extracellular fluid (ECF) have the same concentration
of nonpermeating solutes as the ICF. Intravenous fluids
given to patients are usually isotonic solutions, but hypertonic or hypotonic fluids are given for special purposes. A
0.9% solution of NaCl, called normal saline, is isotonic to
human blood cells.
It is important to note that osmolarity and tonicity are
not the same. Urea, for example, is a small organic molecule that easily penetrates plasma membranes. If cells are placed
in 300 mOsm/L urea, urea diffuses into them (down its concentration gradient), water follows by osmosis, and the cells
swell and burst. Thus, 300 mOsm/L urea is not isotonic to
the cells. Sodium chloride, by contrast, penetrates plasma
membranes poorly. In 300 mOsm/L NaCl, there is little
change in cell volume; this solution is isotonic to cells.
Carrier-Mediated Transport
The processes of membrane transport described up to this
point do not necessarily require a cell membrane; they can
occur just as well through artificial membranes. We now,
however, come to processes for which a cell membrane is
essential, because they employ transport proteins to get
through the membrane. Thus, the next two processes are
cases of carrier-mediated transport.
The carriers act like enzymes in some ways: The
solute is a ligand that binds to a specific receptor site on
the carrier, like a substrate binding to the active site of an
enzyme. The carrier exhibits specificity for a certain ligand, just as an enzyme does for its substrate. A glucose carrier, for example, cannot transport fructose. Carriers also
exhibit saturation; as the solute concentration rises, its
rate of transport through a membrane increases, but only
up to a point. When every carrier is occupied, adding more
solute cannot make the process go any faster. The carriers
are saturated—no more are available to handle the
increased demand, and transport levels off at a rate called
the transport maximum (Tm) (fig. 3.17). As we’ll see later in the book, the transport maximum explains why glucose
appears in the urine of people with diabetes mellitus. An
important difference between a membrane carrier and an
enzyme is that carriers do not chemically change their ligands; they simply pick them up on one side of the membrane and release them, unchanged, on the other. There are three kinds of carriers: uniports, symports,
and antiports. A uniport18 carries only one solute at a
time. For example, most cells pump out calcium by means
of a uniport, maintaining a low intracellular calcium concentration so that calcium salts don’t crystallize in their
cytoplasm. A symport19 carries two or more solutes
through a membrane simultaneously in the same direction; this process is called cotransport.20 As an example,
absorptive cells of the small intestine and kidneys take up
sodium and glucose simultaneously by means of a symport. An antiport21 carries two or more solutes in opposite
directions; this process is called countertransport. Cells
everywhere have an antiport called the sodium-potassium
pump that continually removes Na from the cell and
brings in K.
These carriers employ two mechanisms of transport
called facilitated diffusion and active transport. (Any carrier type—uniport, symport, or antiport—can use either
of these transport mechanisms.) Facilitated22 diffusion is
the carrier-mediated transport of a solute through a membrane down its concentration gradient. It is a passive
transport process; that is, it does not consume ATP. It
transports solutes such as glucose that cannot pass
through the membrane unaided. The solute attaches to a
binding site on the carrier, then the carrier changes conformation and releases the solute on the other side of the
membrane (fig. 3.18).
Active transport is the carrier-mediated transport of a
solute through a membrane up its concentration gradient,
using energy provided by ATP. The calcium pumps mentioned previously use active transport. Even though Ca2 is
already more concentrated in the ECF than within the cell,
these carriers pump still more of it out of the cell. Active
transport also enables cells to absorb amino acids that are
already more concentrated in the cytoplasm than in the ECF.
A prominent example of active transport is the
sodium-potassium (Na-K) pump, also known as Na-K
ATPase because the carrier is an enzyme that hydrolyzes
ATP. The Na-K pump binds three Na simultaneously
on the cytoplasmic side of the membrane, releases these
to the ECF, binds two K simultaneously from the ECF,
and releases these into the cell (fig. 3.19). Each cycle of
the pump consumes one ATP and exchanges three Na
for two K. This keeps the K concentration higher and
the Na concentration lower within the cell than in the
ECF. These ions continually leak through the membrane,
and the Na-K pump compensates like bailing out a
leaky boat. Lest you question the importance of the Na-K
pump, about half of the calories you consume each day
are used for this alone. Beyond compensating for a leaky
plasma membrane, the Na-Kpump has at least four
functions:
1. Regulation of cell volume. Certain anions are
confined to the cell and cannot penetrate the
plasma membrane. These “fixed anions,” such as
proteins and phosphates, attract and retain cations.
If there were nothing to correct for it, the retention
of these ions would cause osmotic swelling and
possibly lysis of the cell. Cellular swelling, however,
stimulates the Na-K pumps. Since each cycle of
the pump removes one ion more than it brings in,
the pumps are part of a negative feedback loop that
reduces ion concentration, osmolarity, and cellular
swelling.
2. Secondary active transport. The Na-K pump
maintains a steep concentration gradient of Na
and K between one side of the membrane and the
other. Like water behind a dam that can be tapped
to generate electricity, this gradient has a high
potential energy that can drive other processes.
Since Na has a high concentration outside the
cell, it tends to diffuse back in. Some cells exploit
this to move other solutes into the cell. In kidney
tubules, for example, the cells have Na-K pumps
in the basal membrane that remove Na from the
cytoplasm and maintain a low intracellular Na
concentration. In the apical membrane, the cells
have a facilitated diffusion carrier, the sodiumglucose transport protein (SGLT), which
simultaneously binds Na and glucose and carries
both into the cell at once (fig. 3.20). By exploiting
the tendency of Na to diffuse down its
concentration gradient into these cells, the SGLT
absorbs glucose and prevents it from being wasted
in the urine. The SGLT in itself does not consume
ATP, but it does depend on the ATP-consuming
Na-K pumps at the base of the cell. We say that
glucose is absorbed by secondary active transport,
as opposed to the primary active transport carried
out by the Na-K pump.
3. Heat production. When the weather turns chilly, we
not only turn up the furnace in our home but also
the “furnace” in our body. Thyroid hormone
stimulates cells to produce more Na-K pumps.
As these pumps consume ATP, they release heat,
compensating for the body heat we lose to the cold
air around us.
4. Maintenance of a membrane potential. All living
cells have an electrical charge difference called the
resting membrane potential across the plasma
membrane. Like the two poles of a battery, the inside of the membrane is negatively charged and the
outside is positively charged. This difference stems
from the unequal distribution of ions on the two
sides of the membrane, maintained by the Na-K
pump. The membrane potential is essential to the
function of nerve and muscle cells, as we will study
in later chapters.
Vesicular Transport
So far, we have considered processes that move from one
to a few ions or molecules through the plasma membrane
at a time. Vesicular transport processes, by contrast, move
large particles, droplets of fluid, or numerous molecules at
once through the membrane, contained in bubblelike vesicles of membrane. Vesicular processes that bring matter into
a cell are called endocytosis23 (EN-doe-sy-TOE-sis) and
those that release material from a cell are called exocytosis24 (EC-so-sy-TOE-sis).
There are two basic forms of endocytosis: phagocytosis and pinocytosis. Phagocytosis25 (FAG-oh-sy-TOE-sis),
or “cell eating,” is the process of engulfing particles such
as bacteria, dust, and cellular debris—particles large
enough to be seen with a microscope. Neutrophils (a class
of white blood cells), for example, protect the body from
infection by phagocytizing and killing bacteria. A neutrophil spends most of its life crawling about in the connective tissues by means of blunt footlike extensions
called pseudopods26 (SOO-doe-pods). When a neutrophil
encounters a bacterium, it surrounds it with its
pseudopods and traps it in a phagosome27—a vesicle in
the cytoplasm surrounded by a unit membrane (fig. 3.21).
A lysosome merges with the phagosome, converting it to a
phagolysosome, and contributes enzymes that destroy the
invader. Several other kinds of phagocytic cells are
described in chapter 21. In general, phagocytosis is a way
of keeping the tissues free of debris and infectious
microorganisms. Some cells called macrophages (literally
“big eaters”) phagocytize the equivalent of 25% of their
own volume per hour.
Pinocytosis28 (PIN-oh-sy-TOE-sis), or “cell drinking,” is the process of taking in droplets of ECF containing
molecules of some use to the cell. While phagocytosis
occurs in only a few specialized cells, pinocytosis occurs
in all human cells. The process begins as the plasma membrane becomes dimpled, or caved in, at points. These pits
soon separate from the surface membrane and form small
membrane-bounded pinocytotic vesicles in the cytoplasm. The vesicles contain droplets of the ECF with
whatever molecules happened to be there.
Receptor-mediated endocytosis29 (fig. 3.22) is a
more selective form of either phagocytosis or pinocytosis. It enables a cell to take in specific molecules from the
ECF with a minimum of unnecessary fluid. Particles in
the ECF bind to specific receptors on the plasma membrane. The receptors then cluster together and the membrane sinks in at this point, creating a pit coated with a
peripheral membrane protein called clathrin.
30 The pit
soon pinches off to form a clathrin-coated vesicle in the
cytoplasm. Clathrin may serve as an “address label” on
the coated vesicle that directs it to an appropriate destination in the cell, or it may inform other structures in the
cell what to do with the vesicle.
One example of receptor-mediated endocytosis is the
uptake of low-density lipoproteins (LDLs)—protein-coated
droplets of cholesterol and other lipids in the blood (see
chapter 26). The thin endothelial cells that line our blood
vessels have LDL receptors on their surfaces and absorb
LDLs in clathrin-coated vesicles. Inside the cell, the LDL
is freed from the vesicle and metabolized, and the membrane with its receptors is recycled to the cell surface.
Much of what we know about receptor-mediated endocytosis comes from studies of a hereditary disease called
familial hypercholesterolemia, which dramatically illustrates the significance of this process to our cardiovascular health
Insight 3.3
Clinical Application
Familial Hypercholesterolemia
The significance of LDL receptors and receptor-mediated endocytosis is
illustrated by a hereditary disease called familial hypercholesterolemia.31 People with this disease have an abnormally low number
of LDL receptors. Their cells therefore absorb less cholesterol than normal, and the cholesterol remains in the blood. Their blood cholesterol
levels may be as high as 1,200 mg/dL, compared to a normal level of
about 200 mg/dL. People who inherit the gene from both parents typically have heart attacks before the age of 20 (sometimes even in
infancy) and seldom survive beyond the age of 30.Endothelial cells also imbibe insulin by receptormediated endocytosis. Insulin is too large a molecule to
pass through channels in the plasma membrane, yet it must
somehow get out of the blood and reach the surrounding
cells if it is to have any effect. Endothelial cells take up
insulin by receptor-mediated endocytosis, transport the
vesicles across the cell, and release the insulin on the other
side, where tissue cells await it. Such transport of a substance across a cell (capture on one side and release on the
other side) is called transcytosis32 (fig. 3.23). Receptormediated endocytosis is not always to our benefit; hepatitis, polio, and AIDS viruses “trick” our cells into engulfing
them by receptor-mediated endocytosis Exocytosis (fig. 3.24) is the process of discharging
material from a cell. It occurs, for example, when endothelial cells release insulin to the tissue fluid, breast cells
secrete milk, gland cells release hormones, and sperm
cells release enzymes for penetrating an egg. It bears a
superficial resemblance to endocytosis in reverse. A secretory vesicle in the cell migrates to the surface and “docks”
on peripheral proteins of the plasma membrane. These
proteins pull the membrane inward and create a dimple
that eventually fuses with the vesicle and allows it to
release its contents.
The question might occur to you, If endocytosis continually takes away bits of plasma membrane to form intracellular vesicles, why doesn’t the membrane grow smaller
and smaller? Another purpose of exocytosis, however, is
to replace plasma membrane that has been removed by
endocytosis or become damaged or worn out. Plasma
membrane is continually recycled from the cell surface
into the cytoplasm and back to the surface.
Table 3.3 summarizes the mechanisms of transport
we have discussed.
The Cytoplasm
Objectives
When you have completed this section, you should be able to
• list the main organelles of a cell, describe their structure, and
explain their functions;
• describe the cytoskeleton and its functions; and
• give some examples of cell inclusions and explain how
inclusions differ from organelles.We now probe more deeply into the cell to study the structures in the cytoplasm. These are classified into three
groups—organelles, cytoskeleton, and inclusions—all
embedded in the clear, gelatinous cytosol.
Organelles
Organelles are internal structures of a cell that carry out specialized metabolic tasks. Some are surrounded by one or
two layers of unit membrane and are therefore referred to as
membranous organelles. These are the nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, and
Golgi complex. Organelles that are not surrounded by membranes include the ribosomes, centrosome, centrioles, and
basal bodies.
The Nucleus
The nucleus is the largest organelle and usually the only
one visible with the light microscope. It is usually spheroid
to elliptical in shape and typically about 5 m in diameter.
Most cells have a single nucleus, but there are exceptions.
Mature red blood cells have none; they are anuclear. A few
cell types are multinucleate—having 2 to 50 nuclei—
including some liver cells, skeletal muscle cells, and certain bone-dissolving and platelet-producing cells.
With the TEM, the nucleus can be distinguished by
the two unit membranes surrounding it, which together
form the nuclear envelope (fig. 3.25). The envelope is perforated with nuclear pores, about 30 to 100 nm in diameter, formed by a ring of proteins. These proteins regulate
molecular traffic through the envelope and act like a rivet
to hold the two unit membranes together. Hundreds of
molecules pass through the nuclear pores every minute.
Coming into the nucleus are raw materials for DNA and
RNA synthesis, enzymes that are made in the cytoplasm
but function in the nucleus, and hormones that activate
certain genes. Going the other way, RNA is made in the
nucleus but leaves to perform its job in the cytoplasm.
The material in the nucleus is called nucleoplasm.
This includes chromatin33 (CRO-muh-tin)—fine threadlike matter composed of DNA and protein—and one or
more dark-staining masses called nucleoli (singular,
nucleolus), where ribosomes are produced. The genetic
function of the nucleus is described in chapter 4.
Endoplasmic Reticulum
Endoplasmic reticulum (ER) literally means “little network within the cytoplasm.” It is a system of interconnected channels called cisternae34 (sis-TUR-nee) enclosed
by a unit membrane (fig. 3.26). In areas called rough endoplasmic reticulum, the network is composed of parallel,
flattened sacs covered with granules called ribosomes.
The rough ER is continuous with the outer membrane of
the nuclear envelope, and adjacent cisternae are often connected by perpendicular bridges. In areas called smooth
endoplasmic reticulum, the membrane lacks ribosomes,
the cisternae are more tubular in shape, and they branch
more extensively. The cisternae of the smooth ER are
thought to be continuous with those of the rough ER, so the
two are functionally different parts of the same network.
The ER synthesizes steroids and other lipids, detoxifies alcohol and other drugs, and manufactures all of the
membranes of the cell. Rough ER produces the phospholipids and proteins of the plasma membrane, and synthesizes proteins that are either packaged in other
organelles such as lysosomes or secreted from the cell.
Rough ER is most abundant in cells that synthesize large
amounts of protein, such as antibody-producing cells
and cells of the digestive glands. This role is discussed
further in chapter 4.
Most cells have only a scanty smooth ER, but it is relatively abundant in cells that engage extensively in detoxification, such as liver and kidney cells. Long-term abuse
of alcohol, barbiturates, and other drugs leads to tolerance
partly because the smooth ER proliferates and detoxifies
the drugs more quickly. Smooth ER is also abundant in
cells of the testes and ovaries that synthesize steroid hormones. Skeletal muscle and cardiac muscle contain extensive networks of smooth ER that store calcium and release
it to trigger muscle contraction.
Ribosomes
Ribosomes are small granules of protein and RNA found
in the nucleoli, in the cytosol, and on the outer surfaces of
the rough ER and nuclear envelope. They “read” coded
genetic messages (messenger RNA) and assemble amino
acids into proteins specified by the code. This process is
detailed in chapter 4.
Golgi Complex
The Golgi35 (GOAL-jee) complex is a small system of cisternae that synthesize carbohydrates and put the finishing
touches on protein and glycoprotein synthesis. The complex resembles a stack of pita bread. Typically, it consists
of about six cisternae, slightly separated from each other;
each cisterna is a flattened, slightly curved sac with
swollen edges (fig. 3.27). The Golgi complex receives the
newly synthesized proteins from the rough ER. It sorts
them, cuts and splices some of them, adds carbohydrate
moieties to some, and finally packages the proteins in
membrane-bounded Golgi vesicles. These vesicles bud off the swollen rim of a cisterna and are seen in abundance in
the neighborhood of the Golgi complex. Some vesicles
become lysosomes, the organelle discussed next; some
migrate to the plasma membrane and fuse with it, contributing fresh protein and phospholipid to the membrane; and some become secretory vesicles that store a cell
product, such as breast milk or digestive enzymes, for later
release. The role of the Golgi complex in protein synthesis
and secretion is detailed in chapter 4.
Lysosomes
A lysosome36 (LY-so-some) (fig. 3.28a) is a package of
enzymes bounded by a single unit membrane. Although
often round or oval, lysosomes are extremely variable in
shape. When viewed with the TEM, they often exhibit
dark gray contents devoid of structure, but sometimes
show crystals or parallel layers of protein. At least 50 lysosomal enzymes have been identified. They hydrolyze proteins, nucleic acids, complex carbohydrates, phospholipids, and other substrates. In the liver, lysosomes break
down stored glycogen to release glucose into the blood stream. White blood cells use their lysosomes to digest
phagocytized bacteria. Lysosomes also digest and dispose
of worn-out mitochondria and other organelles; this
process is called autophagy37 (aw-TOFF-uh-jee). Some
cells are meant to do a certain job and then die. The uterus,
for example, weighs about 900 g at full-term pregnancy
and shrinks to 60 g within 5 or 6 weeks after birth. This
shrinkage is due to autolysis,38 the digestion of surplus
cells by their own lysosomal enzymes. Such programmed
cell death is further discussed in chapter 5.
Peroxisomes
Peroxisomes (fig. 3.28b) resemble lysosomes but contain
different enzymes and are not produced by the Golgi complex. They occur in nearly all cells but are especially
abundant in liver and kidney cells. Peroxisomes neutralize free radicals and detoxify alcohol and other drugs.
They are named for the hydrogen peroxide (H2O2) they
produce in the course of detoxifying alcohol and killing
bacteria. They break down excess H2O2 with an enzyme called catalase. Peroxisomes also decompose fatty acids
into two-carbon acetyl groups, which the mitochondria
then use as an energy source for ATP synthesis.
Mitochondria
Mitochondria39 (MY-toe-CON-dree-uh) (fig. 3.29) are
organelles specialized for synthesizing ATP. They have a
variety of shapes: spheroid, rod-shaped, bean-shaped, or
threadlike. Like the nucleus, a mitochondrion is surrounded by a double unit membrane. The inner membrane
usually has folds called cristae40 (CRIS-tee), which project
like shelves across the organelle. The space between the
cristae, called the matrix, contains ribosomes, enzymes
used in ATP synthesis, and a small, circular DNA molecule called mitochondrial DNA (mtDNA). Mitochondria are the “powerhouses” of the cell. Energy is not made
here, but it is extracted from organic compounds and
transferred to ATP, primarily by enzymes located on the
cristae. The role of mitochondria in ATP synthesis is
explained in detail in chapter 26, and some evolutionary
and clinical aspects of mitochondria are discussed at the
end of this chapter (see insight 3.4).
Centrioles
A centriole (SEN-tree-ole) is a short cylindrical assembly of
microtubules, arranged in nine groups of three microtubules each (fig. 3.30). Two centrioles lie perpendicular to
each other within a small clear area of cytoplasm called the
centrosome41 (see fig. 3.5). They play a role in cell division
described in chapter 4. Each basal body of a flagellum or
cilium is a single centriole oriented perpendicular to the
plasma membrane. Basal bodies originate in a centriolar
organizing center and migrate to the plasma membrane.
Two microtubules of each triplet then elongate to form the
nine pairs of peripheral microtubules of the axoneme. A
cilium can grow to its full length in less than an hour.
The Cytoskeleton
The cytoskeleton is a collection of protein filaments and
cylinders that determine the shape of a cell, lend it structural support, organize its contents, move substances
through the cell, and contribute to movements of the cell
as a whole. It can form a very dense supportive scaffold in
the cytoplasm (fig. 3.31). It is connected to integral proteins of the plasma membrane, and they in turn are connected to protein fibers external to the cell, so there is a
strong structural continuity from extracellular material to
the cytoplasm. Cytoskeletal elements may even connect to
chromosomes in the nucleus, enabling physical tension
on a cell to move nuclear contents and mechanically stimulate genetic function.
The cytoskeleton is composed of microfilaments,
intermediate filaments, and microtubules. Microfilaments
are about 6 nm thick and are made of the protein actin. They
form a network on the cytoplasmic side of the plasma membrane called the membrane skeleton. The phospholipids of
the plasma membrane spread out over the membrane skeleton like butter on a slice of bread. It is thought that the phospholipids would break up into little droplets without this
support. The roles of actin in supporting microvilli and producing cell movements were discussed earlier. In conjunction with another protein, myosin, microfilaments are also
responsible for muscle contraction.
Intermediate filaments (8–10 nm in diameter) are
thicker and stiffer than microfilaments. They resist
stresses placed on a cell and participate in junctions that
attach some cells to their neighbors. In epidermal cells,
they are made of the tough protein keratin and occupy
most of the cytoplasm.
A microtubule (25 nm in diameter) is a cylinder made
of 13 parallel strands called protofilaments. Each protofilament is a long chain of globular proteins called tubulin
(fig. 3.32). Microtubules radiate from the centrosome and
hold organelles in place, form bundles that maintain cell
shape and rigidity, and act somewhat like railroad tracks to
guide organelles and molecules to specific destinations in
a cell. They form the axonemes of cilia and flagella and are
responsible for their beating movements. They also form
the mitotic spindle that guides chromosome movement
during cell division. Microtubules are not permanent
structures. They come and go moment by moment as tubulin molecules assemble into a tubule and then suddenly
break apart again to be used somewhere else in the cell.
The double and triple sets of microtubules in cilia, flagella,
basal bodies, and centrioles, however, are more stable.
Inclusions
Inclusions are of two kinds: stored cellular products
such as glycogen granules, pigments, and fat droplets
(see fig. 3.26b), and foreign bodies such as dust particles,
viruses, and intracellular bacteria. Inclusions are never
enclosed in a unit membrane, and unlike the organelles
and cytoskeleton, they are not essential to cell survival.
The major features of a cell are summarized in table 3.4.Insight 3.4
Evolutionary Medicine
Mitochondria—Evolution and
Clinical Significance
It is virtually certain that mitochondria evolved from bacteria that
invaded another primitive cell, survived in its cytoplasm, and became
permanent residents. Certain modern bacteria called ricketsii live in
the cytoplasm of other cells, showing that this mode of life is feasible.
The two unit membranes around the mitochondrion suggest that the
original bacterium provided the inner membrane and the host cell’s
phagosome provided the outer membrane when the bacterium was
phagocytized.
Several comparisons show the apparent relationship of mitochondria to bacteria. Their ribosomes are more like bacterial ribosomes than
those of eukaryotic (nucleated) cells. Mitochondrial DNA (mtDNA) is a
small, circular molecule that resembles the circular DNA of other bacteria, not the linear DNA of the cell nucleus. It replicates independently
of nuclear DNA. mtDNA codes for some of the enzymes employed in
ATP synthesis. It consists of 16,569 base pairs (explained in chapter 4),
comprising 37 genes, compared to over a billion base pairs and about
35,000 genes in nuclear DNA.
When a sperm fertilizes an egg, any mitochondria introduced by the
sperm are quickly destroyed and only those provided by the egg are
passed on to the developing embryo. Therefore, all mitochondrial DNA
is inherited exclusively through the mother. While nuclear DNA is
reshuffled in every generation by sexual reproduction, mtDNA remains
unchanged except by random mutation. Biologists and anthropologists
have used mtDNA as a “molecular clock” to trace evolutionary lineages
in humans and other species. mtDNA has also been used as evidence in
criminal law and to identify the remains of soldiers killed in action.
mtDNA was used recently to identify the remains of the famed bandit
Jesse James, who was killed in 1882. Anthropologists have gained evidence, although still controversial, that of all the women who lived in
Africa 200,000 years ago, only one has any descendents still living
today. This “mitochondrial Eve” is ancestor to us all.
mtDNA is very exposed to damage from free radicals normally generated in mitochondria by aerobic respiration. Yet unlike nuclear DNA,
mtDNA has no effective mechanism for repairing damage. Therefore, it
mutates about ten times as rapidly as nuclear DNA. Some of these
mutations are responsible for rare hereditary diseases. Tissues and
organs with the highest energy demands are the most vulnerable to
mitochondrial dysfunctions—nervous tissue, the heart, the kidneys,
and skeletal muscles, for example. Mitochondrial myopathy is a degenerative muscle disease in which the muscle displays “ragged red fibers,cells with abnormal mitochondria that stain red with a particular histological stain. Mitochondrial encephalomyopathy, lactic acidosis, and
strokelike episodes (MELAS) is a mitochondrial disease involving
seizures, paralysis, dementia, muscle deterioration, and a toxic accumulation of lactic acid in the blood. Leber hereditary optic neuropathy
(LHON) is a form of blindness that usually appears in young adulthood
as a result of damage to the optic nerve. Kearns-Sayre syndrome (KSS)
involves paralysis of the eye muscles, degeneration of the retina, heart
disease, hearing loss, diabetes, and kidney failure. Damage to mtDNA
has also been implicated as a possible factor in Alzheimer disease,
Huntington disease, and other degenerative diseases of old age.
