The Cell

1
2

The Cell 1-1

The Cell

1. Centrioles
2. Microvillus
3. Rough endoplasmic reticulum
4. Smooth endoplasmic reticulum
5. Mitochondrion
6. Nucleus
7. Golgi complex

Comment: The cell is the fundamental structural and functional unit

of all living organisms. The body contains about 60 × 1012 cells, of
which there are approximately 200 different types. Cells vary widely
in size and shape. A typical cell has polarized compartments and
surface specializations; internal cell structure is modified to reflect
function. The centrally placed nucleus is surrounded by endoplasmic
reticulum. Mitochondria occupy the basal compartment, and the
apical compartment contains the Golgi complex and a centriole.
Apical microvilli increase the plasma membrane surface area for
absorption.

Electron microscopy (EM), as an adjunct to conventional

histology, has advanced our knowledge of the cell and its organelles,
and is an important tool in ultrastructural pathology. In many
cases, EM is essential for definitive diagnosis of disease, such as the
detection and recognition of some neoplastic tumors. It also
provides valuable information on infectious diseases, metabolic
disorders, and helps to determine the ultimate course of medical
treatment.

A composite cell cut open to show organization of its main

components as seen via electron microscopy

The Cell See Book 1.1

 Cell Junctions

1 2

3 4

The Cell 1-2

Cell Junctions

1. Plasma (cell) membrane

2. Gap (communicating) junction
3. Connexin monomer
4. Hydrophilic channel (pore)
5. Connexon (hexamer)

Comment: Metabolic, ionic, and low-resistance electrical

communication occurs between adjacent cells via gap
(communicating) junctions, in which a narrow gap of about 2 nm
separates opposing cell membranes. They are specialized sites
composed of large, tightly packed intercellular channels, which
connect cytoplasm of adjacent cells. Each cylindrical channel,
10-12 nm long and 2.8-3.0 nm in diameter, consists of a pair of
half-channels, termed connexons, which are embedded in the cell
membranes. Each connexon comprises six symmetric protein
subunits, called connexins, that are transmembrane proteins
surrounding a small central aqueous pore (diameter: 1.5-2.0 nm).

Several diseases result from mutations in genes encoding

connexins, which are named according to molecular size. Recessive
mutations in connexin-26, with a molecular size of 26 kD, lead to the
most common cause of inherited human deafness, which often
affects the elderly. Connexin-26 is usually involved in K+ transport in
cells that support cochlear hair cells.

EM of a gap junction in cardiac muscle at low and high magnification,

and schematic of a gap junction

The Cell See Book 1.7

 Nucleus

The Cell 1-3

Nucleus

1. Heterochromatin
2. Nuclear envelope
3. Euchromatin

Comment: The nucleus is the largest, most conspicuous structure

in the cell. Most cells have 1 nucleus. The nucleus consists of the
nucleolus, chromatin, nuclear matrix, and nuclear envelope. A nuclear
envelope encloses the nucleus of interphase cells and separates
nucleus from cytoplasm. The nucleus contains genetic material (DNA)
that is either packed or unpacked. Heterochromatin is the packed
form, whereas euchromatin is the unpacked form. Histone proteins
are involved in packaging of DNA into heterochromatin. Euchromatin
represents unwound DNA in the process of transcription. The
proportion of heterochromatin to euchromatin gives an indication of
the general activity of the cell. Mature erythrocytes of most mammals
do not contain nuclei since they are extruded during development.

Histopathology uses changes in nuclear morphology as diagnostic

features. Many cellular disorders show an increase in nuclear-to-
cytoplasmic ratio, nuclear indentation, ground glass appearance,
crystalloid inclusions, or abnormal multinucleation. Aberrant nuclear
location in a cell may also indicate cellular pathology or injury, such
as the presence of centrally located nuclei in skeletal muscle fibers
of patients with muscular dystrophy.

EM of a lymphocyte

The Cell See Book 1.8

 Nucleus

4
1

2 3

The Cell 1-4

Nucleus

1. Nuclear envelope
2. Nuclear pore (complex)
3. Perinuclear space
4. Nucleus (with heterochromatin)
5. Cytoplasm (Cytosol)
6. Rough endoplasmic reticulum (RER)

Comment: A nuclear envelope encloses the nucleus of interphase

cells and separates nucleus from cytoplasm. It consists of two
parallel unit membranes separated by a narrow space (10-70 nm
wide) termed the perinuclear space (cisterna). Many small octagonal
apertures, called nuclear pores, perforate the envelope. About
100 nm in diameter, they permit selective, bidirectional exchange of
small molecules, ribosomal subunits, and other substances between
nucleus and cytoplasm. The outer rim of each pore forms by fusion
of outer and inner nuclear membranes. A nuclear pore complex
spanning the opening of each pore consists of eight proteins, or
nucleoporins, around a central plug or granule.

The number and distribution of nuclear pore complexes vary widely

according to activity and type of cell; they are especially numerous in
metabolically active cells. Genetic mutations in the nucleoporin,
ALADIN, have been linked to the autosomal recessive Triple-A
(Allgrove) syndrome, also known as Achalasia-Addisonianism-
Alacrimia syndrome.

EM of a nuclear envelope, and schematic of a nuclear pore complex

The Cell See Book 1.10

 Mitochondria

1 2 3 4

The Cell 1-5

Mitochondria

1. Rough endoplasmic reticulum (RER)

2. Cristae
3. Mitochondrial matrix
4. Outer mitochondrial membrane

Comment: Mitochondrial shape varies with plane of section and

type of cell. Each organelle has thin, shelf, or tubular cristae that
project into the mitochondrial matrix. The outer mitochondrial
membrane has a smooth contour. It consists mostly of the large
channel-forming protein—porin—which increases membrane
permeability for passage of molecules and metabolites required for
ATP synthesis. The inner mitochondrial membrane is thrown into a
series of transverse shelf-like or tubular folds known as cristae. The
mitochondrial matrix has an increased electron density that is finely
granular.

Mitochondrial myopathies are a group of diseases that result

primarily in muscle weakness and dysfunction. They are typically
inherited disorders, which vary from mild to life threatening. They are
caused by mutations in mitochondrial DNA, of which there are over
50 harmful mutations. The most common symptoms are severe
muscle weakness, cramps, spasm, and cardiac involvement.

Schematic of mitochondria and EM of mitochondria in a hepatocyte

The Cell See Book 1.11

 Ribosomes

The Cell 1-6

Ribosomes

1. Cisterna of rough endoplasmic reticulum (RER)

2. Ribosome
3. Polyribosome

Comment: Ribosomes are small, spherical, electron-dense particles

that synthesize proteins. They are uniform in size, about 15 to 20 nm
in diameter, and consist mostly of RNA and associated proteins.
Free ribosomes in the cytoplasm occur as single particles or rosette-
like clusters, known as polyribosomes, which consist of several
ribosomes arranged along a thread of messenger RNA (mRNA).
Single ribosomes are inactive, whereas polyribosomes are active in
protein synthesis, where they assemble specific amino acids into
polypeptides. Ribosomes may be attached to membranes of the
rough-surfaced endoplasmic reticulum (RER) or to the outer nuclear
membrane. Polyribosomes synthesize proteins for internal use by the
cell, whereas ribosomes attached to the RER engage in protein
synthesis for export from the cell or for proteins destined for
lysosomes.

Antibiotics are used clinically to treat bacterial infections. Many

such pharmaceuticals inhibit the proliferation of infectious bacteria by
targeting the ribosome. They bind to specific regions of the large or
small subunit, interfering with translation and protein synthesis in the
pathogen. Antibiotic resistance has become a serious public health
problem around the world.

EM of part of an active fibroblast and higher magnification EM of part

of a protein-synthesizing cell

The Cell See Book 1.15

 Golgi Complex

The Cell 1-7

Golgi Complex

1. Trans-surface of Golgi complex

2. Saccule of medial compartment
3. Cis-surface of Golgi complex
4. Golgi vesicles

Comment: The Golgi complex (or apparatus) is a complex array of

flattened, slightly curved, closely packed membrane-bound sacs.
This highly polarized, compartmentalized organelle has convex and
concave sides and 3 functionally distinct compartments: a cis-Golgi
network of vesicles on the convex side, a medial compartment of
stacks of flattened saccules, and on the concave side a trans-Golgi
network of vesicles and vacuoles for distribution and sorting of
secretory products. Each saccule in the medial compartment
contains a different group of processing enzymes that reside in its
membranes as integral membrane proteins. Some cells have 1 Golgi
complex; others, which actively synthesize proteins and
polysaccharides, have many. The Golgi complex adds proteins to
sugars to form glycoproteins, assembles polysaccharides, elaborates
membrane lipids, and produces lysosomes that are kept by cells.

Disassembly of the Golgi complex occurs in cells undergoing

apoptosis (or programmed cell death) whereby extensive and
irreversible fragmentation of this organelle forms small tubulo-
vesicular components. This feature is probably due to a caspase-
related cleavage of integral Golgi tethering proteins. Caspases are
proteases in the cytoplasm that become activated early in apoptosis.

Schematic and high-magnification EM of the Golgi complex showing

its functional compartments

The Cell See book 1.16 and 1.17

 Cytoplasm

1 2 3

5 4

The Cell 1-8

Cytoplasm

1. Nucleus
2. Golgi complex
3. Mitochondria
4. Glycogen
5. Peroxisome

Comment: The cytoplasm is a complex aqueous gel made of water

(about 70%), proteins, lipids, carbohydrates, and organic and
inorganic molecules. Organelles and inclusions are in the cytoplasm.
Electron-dense glycogen particles within the cytoplasm form
aggregates and are not membrane-bound. Peroxisomes are
enveloped by a single membrane and contain crystalline or strand-
like deposits. Mitochondria are distinguished from peroxisomes by an
inner and outer membrane.

Zellweger (or cerebrohepatorenal) syndrome is a pero xisomal

disorder that usually leads to abnormalities in the brain, kidneys, and
liver. Affected infants die soon after birth, which is most likely due to
faulty neural cell myelination in utero.

EM of peroxisomes in a liver hepatocyte

The Cell See Book 1.19

 Inclusions

2 1

The Cell 1-9

Inclusions

1. Glycogen rosettes
2. Rough endoplasmic reticulum (RER)
3. Mitochondria

Comment: Glycogen—a cytoplasmic inclusion—appears as small,

electron-dense particles (20 to 40 nm in diameter). They are free in
the cytoplasm and are not membrane-bound. Aggregates of
glycogen particles form irregular patches known as alpha particles
(or rosettes). Glycogen—a d-glucose polymer—is stored mostly in
the cytoplasm of hepatocytes of the liver and skeletal muscle fibers.
It also occurs in smaller amounts in cells of other tissues. Synthesis,
storage, and breakdown of glycogen occur rapidly according to
need. By light microscopy, glycogen can be visualized with the
periodic acid-Schiff stain.

Glycogen storage disease (GSD) is a group of more than 10

inherited “inborn errors of metabolism” that affect the synthesis or
breakdown of glycogen. These autosomal recessive disorders
typically occur in childhood.

von Gierke disease (or Type I GSD) is a deficiency of the enzyme

glucose-6-phosphatase. It leads to an abnormal accumulation of
glycogen in muscle and liver cells, which causes clinically significant
end-organ disease and morbidity.

High-magnification EM of glycogen rosettes in a hepatocyte

The Cell See Book 1.20

 Cytoplasmic Vesicles

3
4

The Cell 1-10

Cytoplasmic Vesicles

1. Caveolae
2. Cytoplasmic vesicle
3. Plasma membrane
4. Basement membrane

Comment: Cells have several kinds of membrane-bound vesicles

that form by invaginations of plasma membrane. They then enter the
cytoplasm by pinching off from the surface and are transported to
other parts of the cell. Many caveolae in endothelial cells mediate
transcytosis, whereby vesicles derived from caveolae are taken
across a cell and release their contents at another surface. Other
kinds of cytoplasmic vesicles, most derived from the Golgi complex,
engage in exocytosis. Vesicles move to the cell surface, fuse with
plasma membrane, and discharge contents to the cell exterior.

Familial hypercholesterolemia is an autosomal dominant disorder

caused by a mutation in the gene on chromosome 19 that encodes
the LDL receptors. The defective receptors lose their affinity for
coated pits, and cellular uptake of cholesterol is blocked. This
causes a severe elevation in serum cholesterol, which may lead to
premature atherosclerotic lesions in the walls of blood vessels, such
as the coronary arteries.

EM of caveolae and vesicles in an endothelial cell of a capillary

The Cell See Book 1.22

 Cytoskeleton

The Cell 1-11

Cytoskeleton

1. Microtubules
2. Mitochondrion

Comment: Microtubules are hollow, semirigid cylindrical organelles

of uniform diameter (25 nm) but extremely variable in length and are
particularly abundant in neurons, platelets, leukocytes, and dividing
cells. They form a major component of the cytoskeleton by helping
to provide mechanical strength and establish cell shape. They
engage in intracellular transport of organelles (such as mitochondria
and cytoplasmic vesicles), ciliary and flagellar motility, mitotic spindle
formation, chromosome translocation, and cytokinesis during cell
division. They are not bound by a membrane, and their walls are
composed of linear polymers (or protofilaments) of the globular
protein, tubulin. Microtubules are the main constituent of cilia,
flagella, and centrioles.

Microtubule targeting drugs, such as Taxol and Vinblastine, are

used in cancer therapies to treat many human malignancies. They
prevent mitotic spindle formation in tumor cells by inhibiting cell
division at the metaphase/anaphase transition. Whereas taxol mainly
acts to stabilize microtubules, vinblastine blocks mitosis by
depolymerizing microtubules.

EM of microtubules in a cultured cell

The Cell See Book 1.23