AROUND 350 years ago, the French philosopher René Descartes concluded
that the human body works on mechanical principles. He compared the illness and
discomfort caused by diseased organs to the way in which a machine grinds to a
halt when a single part breaks down. He reasoned that all machines can be
restored to working order by simply mending the broken component, and believed
that the same was true of our own bodies. This mechanistic view, which treats
the body as a sum of organs and tissues, still dominates Western medicine. Even
so, we rarely, if ever, think of the 75 million million tiny components, or
cells, we are composed of, which range in size from three hundredths of a
millimetre to one millimetre in diameter (30—1000 micrometres).
Not all organisms are made of millions of cells. Some animals, like hydra (an
invertebrate), contain only a few thousand, and even tinier organisms comprise
one cell alone. Also, cells vary greatly depending on their function and where
they live. In animals, for example, nerve cells (neurons) have specialised
extensions and a large surface area to propagate electrical impulses (Inside
Science No. 19), muscle cells use tiny protein filaments to contract and
withstand high pressure (Inside Science No. 71), and white blood cells can
protect the body by engulfing invading pathogens (Inside Science No. 7).
Despite this multitude of cellular shapes and structures, nearly all cells
share three fundamental features: first, a cell membrane—the outermost
layer that envelopes the cell’s contents; second, the genetic information
encoded in deoxyribonucleic acid (DNA) that directs the cell’s activities; and
third, the cytoplasm—the material within the cell membrane apart from the
nucleus, consisting of a jelly-like substance (cytosol) rich in nutrients and
all the biochemicals necessary for cell life.
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For about a billion years, the Earth was probably lifeless, and in its
crevices and valleys there bubbled nothing more than a rudimentary chemical
stew. According to two biochemists, the American Stanley Miller and the Russian
Alexander Oparin, the ingredients of this “primordial soup” gradually reacted
and changed into more complex chemical forms as a result of exposure to
lightning, volcanic eruptions, torrential rains and other environmental
influences. Eventually, around 3.5 billion years ago, these complex chemicals
acquired the ability to make copies of themselves—the first life forms had
arrived. These evolved into the first simple cells, now known as prokaryotes.
Prokaryotes, pretty much unchanged, still abound on Earth today. They alone
reigned for over half a billion years, until some evolved into a more elaborate
form of cell: the eukaryote.
Eukaryotic cells dwarf even the largest prokaryotes—imagine a cat and a
flea and you will have some idea of their relative sizes. They guard their
genetic information, DNA, within a protective double membrane to form a nucleus.
Inside, the DNA is tightly organised into thread-like structures called
chromosomes. Prokaryotic DNA, in contrast, floats free in the cytoplasm. Perhaps
the most conspicuous difference between the two cell types is the medley of
highly organised structures, or organelles, that oversee the daily workings of
eukaryotic cells. Prokaryotic cells contain only a few simple non-membranous
organelles (see Box 1).
Just as the organs of the body perform their own tasks, so do organelles
within the cytoplasm. They demarcate different aspects of cellular activity and
ensure that products and raw materials for each process do not mix. The position
of organelles permits the ordered transfer of substances along a “production
line”, like the passage of food through the stomach, small intestine and colon
of the gut.
Unsurprisingly, since proteins are the building blocks of all organisms, most
organelles are involved in constructing and sorting them. A basic
protein-producing apparatus is common to all cells, and the instructions needed
to make proteins are contained in DNA. During protein synthesis, subunits of
messenger RNA (mRNA), read and transcribe a stretch of DNA, joining together to
make a template which can then be used in the next stage of the manufacturing
process. In eukaryotes, the completed mRNA molecule floats through a pore in the
nuclear membrane and latches onto a spherical structure called a ribosome. Here,
amino acids (the subunits of protein) link together in the specific sequence
spelt out in the mRNA template.
Ribosomes are composed of half RNA, half protein, and exist either free in
the cytosol or attached to membranes. They originate from a dense patch in the
nucleus called the nucleolus. Eukaryotic ribosomes are heavier and more complex
than prokaryotic ribosomes, although they perform identical tasks. Ribosomes
often cluster together into “polysomes“, where they churn out proteins in
conveyor-belt style.
The only other cytoplasmic structures that prokaryotes have in common with
eukaryotes are the granules they use to store carbohydrate, which hungry cells
break down when they require energy. Animal cells store carbohydrate as
glycogen, whereas plant cells use starch. Both types of granule are long chains
or polymers of the sugar molecule glucose, coiled up into pellets.
That, however, is where the similarities end. One of the advances that
eukaryotes have made over prokaryotes is the internal scaffolding of protein
fibres, or cytoskeleton, which they use to organise and reinforce the expanded
cytoplasm. This cellular fortification consists of several types of fibres. Some
are stiff hollow rods constructed from tubulin protein. These “microtubules” are
used to fix organelles in place and to move them around the cell. Others consist
of subunits of actin (a protein). Actin subunits perpetually join and leave
their chains, so lengthening and shortening them, allowing cells to continually
change shape. And microfilaments may hook onto the inside of the cell membrane
to aid cell migration—during organ formation in growing embryos—or
to shuffle materials around the cytoplasm. In muscle cells, filaments of actin
and myosin (another protein) form the machinery that drives muscle contraction
(Inside Science No. 71).
Microtubules are also the main components of hair-like structures that
protrude from the cell, known as cilia and flagella. These are used to propel
cells along, or to move substances over their exterior. Flagella work alone, and
as a consequence are on average 10 to 20 times longer than cilia. Tiny creatures
that live in ponds, like the unicellular Euglena, travel with the aid
of a long, waggling flagellum, as do sperm. Millions of cilia commonly line
ducts and tubules in larger organisms, where they sweep substances along. For
example, cells lining the lungs use cilia to drive mucus and impurities towards
the nasal passages.
Membranes
Protein processing
THOUSANDS of structures with membranes crowd the eukaryotic cytoplasm, the
most numerous being a dense network of interconnected tubes (cisternae), called
the endoplasmic reticulum (ER). There are two types of ER: rough ER (RER),
so-called because its cytoplasmic face is dotted with ribosomes, and smooth ER
(SER), which is devoid of ribosomes.
The RER is more extensive than SER and acts as a protein producer and storage
vessel. Amino acid chains, freshly synthesised by the ribosomes, slide through
tiny holes in its membrane into the cisternae, where they remain until they are
sent elsewhere in the cytoplasm, or to the cell edge where they are secreted or
incorporated into the cell membrane.
The SER produces steroid hormones and other lipids (a collective term for a
group of compounds including fats, waxes and oils). The two types of endoplasmic
network are not joined, so their cargoes do not get confused. RER connects
directly with nuclear pores, through which mRNA molecules for protein
manufacture pass. Cells that generate lots of protein, such as stomach cells
that secrete digestive enzymes, possess an extensive RER. Likewise, cells in the
gonads that produce steroid hormones have a large SER.
Proteins in the RER have a variety of possible destinations. Many are
shuttled to the cell’s sorting and packaging factory, the Golgi apparatus, where
they are prepared for secretion. The Golgi apparatus is made up of between 6 and
20 saucer-shaped membranous sacs stacked on top of each other, surrounded by
tiny membranous containers or vesicles. As the proteins pass through each layer
in the stack, moving progressively closer to the cell margins, they undergo
chemical modification— usually involving the addition of sugar to form
glycoproteins. Many cell secretions, such as mucus, are glycoproteins. As a
result, the endothelial cells that secrete mucus in the lungs and cervix have
well-developed Golgi apparatuses (
Figure 1).
Protein packages
Exo- and endocytosis
PROTEINS travel from the ER through the cisternae of the Golgi apparatus and
to the cell edge in a unique manner. A section of endoplasmic tube containing
the protein snaps off from the rest of the ER network and closes shut
immediately at each end, imprisoning the protein in a vesicle which fuses with a
nearby Golgi compartment, thus transferring its contents. The proteins move from
one Golgi sac to the next in this way, and eventually protein-filled vesicles
are pinched off, ready for secretion. These secretory vesicles often hang around
near the cell boundary, waiting to be expelled. The process of secretion, in
which the vesicle fuses with the outer membrane and releases its cargo to the
outside world, is called exocytosis. Conversely, when the cell membrane swallows
up materials from the outside, this is known as endocytosis.
Cytologists, the biologists who make the cell their special study, have found
that the Golgi apparatus sometimes determines the destination of its freight
with the help of carbohydrate markers, which act as labels. For example, adding
the sugar mannose-6-phosphate to a protein will ensure that it is sent to a
particular organelle called a lysosome (see below). Other sugars may direct a
Golgi product elsewhere, such as the cell membrane. Most targeting is not, in
fact, by sugars but by “signal sequences” in the protein chain. This form of
intracellular labelling is called “protein targeting“. Two cytologists, the
American James Rothman and Swiss Lelio Orci, have shown that vesicles also have
a variety of protein coats that may help to form the vesicle.
Killer rubbish bins
Uninvited guests
NO eukaryote would be complete without an army of cellular “rubbish bins” or
lysosomes. Unlike normal trash cans, lysosomes are full to the brim with a
cocktail of potent enzymes capable of digesting the basic ingredients of
life—nucleic acids (DNA and RNA), protein, carbohydrate and lipids. Their
main job is to digest worn-out organelles and foreign particles. Some white
blood cells, such as phagocytes, use lysosomes to obliterate pathogens.
Leaky lysosomes can cause damage and even kill old cells. Cytologists still
do not know how the membranes of lysosomes resist the digestive power of the
chemicals they contain. However, they do know that the enzymes are activated
only under extremely acidic conditions, and thus remain dormant if they leak out
into the cytosol.
Similar sized, spherical structures called peroxisomes perform a slightly
different task. They hold enzymes (peroxidases) that catalyse reactions where
hydrogen peroxide (H2O2) is a by-product. These enzymes
facilitate important reactions including the breakdown of certain types of
lipid, alcohol and the synthesis of bile acids in the liver. The problem is that
H2O2 is a powerful oxidising agent and toxic to cells. So an
enzyme, catalase, which converts H2O2to harmless hydrogen and
water, is always found in peroxisomes.
Manufacturing and transporting materials is all very well, but what does the
cell do for energy? Round or sausage-shaped organelles called
mitochondria—often referred to as the “power houses of the
cell”—mastermind aerobic respiration (the production of energy in the
presence of oxygen. See Inside Science No. 87). Between 40 and 1000 are found in
the cytoplasm of all eukaryotes. A double membrane encases each mitochondrion,
the inner of the two being heavily folded into long fingers (cristae). Small
bobbles or “stalked particles” protrude from the cristae at regular intervals
and are composed of a string of enzymes, in a precise sequence, that generate
chemical energy. In the inner space, suspended in a jelly-like medium, is a loop
of DNA, some small ribosomes, enzymes and other chemicals needed for
respiration. Mitochondria tend to be numerous in energy-hungry cells, such as
sperm and heart muscle cells.
The American biologist Lynn Margulis has argued ardently for years that
eukaryotic organelles once lived an independent, prokaryotic existence before
being engulfed by larger cells. This is called the endosymbiotic hypothesis. The
existence of a primitive protein-synthesising apparatus (DNA, ribosomes and
certain enzymes) in organelles such as mitochondria and chloroplasts (see Box 3)
supports this claim. Prokaryotes were probably taken up during feeding, but
instead of being digested, they remained in the cytoplasm as uninvited guests,
and eventually became permanent fixtures. Their presence must have been
beneficial to the host in some way. For example, with mitochondria taking over
the generation of chemical energy, and chloroplasts looking after
photosynthesis, it might have left the cell membrane free for other activities,
such as exocytosis and endocytosis.
Advances in our understanding of the structure and working of cells have
always gone hand in hand with technological developments in microscopy and
biochemistry. Before the invention of the electron microscope some 50 years ago,
biologists thought the cell consisted of little more than a nucleus, cytosol and
a smattering of unidentified granules. The intricate world of organelles, or
“ultrastructure”, was barely imagined. Without doubt, similar breakthroughs will
mould our views for years to come.
World of organelles
New medical paths
CYTOLOGY has opened up the world of subcellular pathology, and paved the way
for the treatment of many disorders. For example, cystic fibrosis is caused by
an abnormal channel protein in the outer membrane of cells of the lung and
pancreas. This prevents salt from escaping from cells and leads to dry and
sticky mucus which clogs organs and causes infections. A lung aerosol spray
containing healthy genes is now available that targets and replaces the faulty
gene coding for the specific membrane protein. This development could change the
lot of cystic fibrosis sufferers. Many psychoactive drugs work by stimulating or
delaying the movement of secretory vesicles containing mood altering chemicals
(neurotransmitters) in brain neurons. Similarly, preventing or stalling vesicle
movement in cancer cells could potentially be used against one of our biggest
and most mysterious killers.
* * *
1: Calling all cells
HUMANS, elephants, mice and daisies all share one thing in common—their
building blocks, eukaryotic cells. Every multicellular organism, in fact, is
constructed from them. However, well-adapted single-celled eukaryotes are
commonplace, as a glance into a garden pond will confirm. Paramecium,
for example, is a free-swimming freshwater creature that paddles around with the
aid of its numerous hair-like cilia.
All living things are classified into five common groups or “kingdoms”
according to their characteristics. Three of these groups are multicellular:
animals, plants and fungi. The others encompass the single-celled
±ą˛ą°ůľ±±đłŮľ±±đ˛ő—protista (eukaryotes) and prokaryota (prokaryotes). All bacteria
are prokaryotes.
Bacteria might seem like a primitive aberration of the eukaryote, but
biochemically they are as diverse as their structurally more advanced cousins,
and successfully colonise every known habitat. They manage quite ably without
all the fancy extras that embellish the eukaryotic cytoplasm.
Their main DNA sits loosely folded in a main loop, in direct contact with the
cytosol, surrounded by numerous other small DNA rings (plasmids). Genetic
engineers find plasmids useful, as foreign genes can be slotted into them
(Inside Science No. 66). The ribosomes of prokaryotes are a simpler and more
compact than those of eukaryotes.
Respiration reactions take place on an in-tucking (or mesosome) of the
outermost membrane, which is the functional equivalent of the mitochondrion.
Similarly, photosynthetic bacteria carry tiny spherical bodies (chromatophores)
that contain a pigment that traps sunlight, but they lack the elaborate
machinery of a plant chloroplast.
A cell wall, built from a substance called peptidoglycan, encases the
prokaryote, and this in turn is often enveloped by a slimy capsule that prevents
drying out. Flagella, though not the eukaryotic sort made from microtubules (see
text), facilitate movement. They are fashioned from flagellin protein and shaped
like corkscrews. Instead of waving, they rotate on their axes like mini
propellers.
* * *
2: The cell membrane
AT first glance, the cell membrane seems to be little more than a protective
barrier demarcating the cellular margins. In fact it tightly regulates the
two-way shipment of molecular cargo and performs many other vital functions. It
is extremely thin, flexible and often folded. In extreme cases these folds form
long glove-like “fingers” or microvilli, increasing surface area by up to 20
times. Microvilli are a conspicuous feature of the cells that line the small
intestine, where they increase the rate at which food molecules can be absorbed
into the bloodstream.
All membranes (including those in organelles) are made up of a double layer
of phospholipid molecules (the phospholipid bi-layer). A phospholipid molecule
consists of a phosphate head and lipid tail (
Figure 2
). Phosphates are
hydrophilic, that is they dissolve in water easily, and are consequently
attracted to wet environments. In contrast, lipid tails are
hydrophobic—they shy away from watery mediums. In a membrane, two layers
of phospholipid sit back-to-back, so that the phosphate heads encase the lipid
ends on both sides. This arrangement means that all the molecules are happy: the
phosphate heads can mingle with the aqueous interior and exterior of the cell,
and simultaneously guard the lipid core from contact with the same water-ridden
environments. Cholesterol molecules dot the inside of the fatty membrane
at intervals and, despite an unpopular image, fulfil a vital role by imparting
rigidity and water resistance to the membrane.
Biochemicals such as steroid hormones, oxygen and carbon dioxide dissolve
readily in the inner, oily bulk of the bi-layer, enabling them to diffuse
effortlessly through the membrane along a concentration gradient. As for
molecules which are not soluble in lipids, including sugars, nucleic acids,
amino acids and proteins, protein globules spanning the membrane shuttle them
back and forth. A host of other proteins of various sizes are randomly scattered
throughout the membrane. Depending on their role, they may either rest on the
surface, penetrate right through or be partly embedded in the membrane (see
Figure 2). According to the “fluid mosaic model”, all the molecular constituents
of the membrane are free to float around. Jonathan Singer and Garth Nicolson,
who formulated the model, likened protein molecules to coloured tiles randomly
placed in a shifting mosaic.
Some proteins transport biochemicals in and out of the cell against a
concentration gradient—for example the sodium-potassium pump in the
membranes of nerve cells, which transports potassium and sodium ions (see Inside
Science No. 47). Other proteins act as water pores, as anchors for
microfilaments, or as catalysts (enzymes) for chemical reactions. On the outer
face of the membrane, receptors bind hormones, and proteins linked to sugars act
as markers (antigens) that allow the immune system to distinguish between the
body’s own cells and interlopers such as viruses and bacteria.
* * *
3: Plant cells
ORGANELLES such as chloroplasts, the cell vacuole and the cell wall, are
exclusive to plant cells.
In green plants, disc-shaped chloroplasts oversee photosynthesis (the
conversion of sunlight into chemical energy). Rather like mitochondria,
chloroplasts carry their innards within a double membrane. The photosynthetic
machinery—a collection of membranes bearing enzymes and chlorophyll
pigment— resides in a bed of jelly-like fluid (stroma) analogous to the
mitochondrial matrix.
All plant cells are bounded by an outer, non-living wall which is composed
mainly of cellulose, a polymer of glucose. Bundles of around 2000 cellulose
chains (microfibrils), bound tightly together in a lattice, form a strong
network. The inner or “primary” cell wall is built from the protein pectin. Fine
strands of cytoplasm stream through intermittent gaps in the wall, and connect
up neighbouring cells. Plant cell walls ensure cells stay swollen with water or
“turgid“. They do this by maintaining a constant concentration of dissolved
salts and sugars in the cell by withstanding cellular expansion during water inflow.
Turgid cells keep plants pert and upright (Inside Science No. 18).
Up to 90 per cent of each plant cell is dominated by the cell vacuole. This
is a membranous bag that stores cell sap, a solution of sugars and salts.
- Molecular Biology of the Cell, by Bruce Alberts et al.,
third edition (Garland, New York, 1994) is suitable for a university-level
readership. - Action Science Series: Life Processes, by Joan O’Sullivan (Oxford
University Press,1994) is suitable for a secondary school level readership.