Cell Biology

Cell

 

I   INTRODUCTION

 

Cell is the smallest unit of an organism that can function independently. All living organisms are made of cells and nothing less than a cell can truly be said to be alive. Some microscopic organisms, such as bacteria and protozoa, are single cells whereas animals and plants are composed of many millions of cells built into tissues and organs. Although viruses and cell-free extracts are able to perform many individual functions of a living cell, they lack the capacity shown by cells of independent survival, growth, and replication, and are therefore not considered to be living. Biologists study cells to learn how they are made from molecules and how individual cells cooperate to make an organism as complex as a human being. Before we can fully understand how a healthy human body functions, how it develops and ages, and what goes wrong with it in disease, we need to understand the cells of which it is made.

II    HISTORICAL ORIGINS OF CELL BIOLOGY

 

 

Lymphocytes

Lymphocytes, or white blood cells, are produced in the marrow of bones. The cells are largely responsible for controlling infection within the body, directly attacking antigens, or foreign substances, in the tissues or circulatory system. Following organ transplants, lymphocytes often attack transplanted tissues, causing the transplant to be rejected.

 

The idea that cells are the fundamental building blocks of living organisms—sometimes termed “the cell theory”—is now universally accepted as true. However, this concept did not spring into existence fully formed, as the result of a single discovery. It took many years for the present view of cells to emerge, and there were many false turns and misapprehensions on the way. The word “cell” comes from the Latin cellula, meaning a small room or cubicle, and was first used by Robert Hooke in his book Micrographia, published in 1665. Hooke was describing the air-filled spaces of dead cells in a slice of cork (bark from an oak tree) and certainly did not realize the general importance of his discovery. Nor did many other talented microscopists of the 17th and 18th centuries, such as Antoni van Leeuwenhoek, Nehemiah Grew, Marcello Malpighi, and Jan Swammerdam, who also saw cells in plant or animal tissues, or as free-living organisms. Indeed it was not until 1839 that the combined insight of a botanist, Matthias Schleiden, and a zoologist, Theodor Schwann, led them to pronounce that “…all organisms are composed of essentially like parts, namely of cells”.

The cell theory was still far from complete and many curious notions remained, for example, about the origins of cells. It required the work of many other biologists, such as Bartholemy Dumortier and Robert Remak, to establish the fact that all cells are produced as a result of the division of existing cells. This notion, which has powerful implications for both cell biology and the origins of life, was famously articulated by German biologist Rudolph Virchow in the phrase “Omnis cellula e cellula”, that is, “all cells come from cells”.

Even then, many misconceptions still existed regarding the nature of the cell membrane, the cytoplasm, and the hereditary material, and it was not until well into the 20th century that the contemporary view of cells emerged. Indeed, even today, the amazingly complex internal structure and chemistry of living cells is still not fully understood and contains many secrets yet to be discovered.

III    LOOKING AT CELLS UNDER THE MICROSCOPE

 

The invention of the microscope in the 17th century made cells visible for the first time and, for hundreds of years afterwards, all that was known about cells was discovered using this simple device. Light microscopes are still crucial to the work of cell biologists, although they have improved out of all recognition from the primitive instruments used by Hooke and Leeuwenhoek. Contemporary light microscopes incorporate sophisticated state-of-the-art devices, such as laser light sources, fluorescent optics, and computer-assisted image processing, which reveal detail at the very limit of resolution (down to 0.1 microns or micrometres (µm), each µm being a millionth of a metre). For even higher magnification, electron microscopes, invented in the 1930s, extend this limit by using beams of electrons instead of beams of light as the source of illumination. They greatly extend our ability to see the fine details of cells, and even make some of the larger molecules visible, although they cannot be used with living specimens.

What do you see if you look at cells under a light microscope? If you examine a very thin slice of a suitable plant or animal tissue, for example, you will see it is divided into thousands of small cells. These may be either closely packed or separated from one another by a material known as the extracellular matrix. Each cell will be about 20 µm in diameter. Under the right conditions, the cells in your section will show signs of life, with particles moving around inside them and individual cells slowly changing shape and dividing.

To see more of the internal structure of a cell you need to use special tricks, since cells are not only small but also transparent and colourless (being about 70 per cent water). One approach is to stain the cells in your section with dyes or specific molecular probes that colour particular components. Alternatively, you can exploit the fact that cell components differ slightly from one another in refractive index (just as glass differs from water) and these small differences can be made visible by means of special lenses. In either case, the contrast and resolution of the image can be stored, enlarged, and further enhanced by electronic processing.

IV   GENERAL FEATURES OF CELLS

 

 

Animal Cell

An animal cell typically contains several types of membrane-bound organs, or organelles. The nucleus controls the cell’s activities and stores the genetic information that is carried from generation to generation. The mitochondria generate energy for the cell. Proteins are manufactured by the ribosomes that sit on the rough endoplasmic reticulum. The Golgi apparatus packages, distributes, and exports lipids and proteins, while lysosomes store enzymes for digesting food. The entire cell is wrapped in a lipid membrane that selectively permits materials to pass in and out of the cytoplasm.

 

The microscope shows us that cells exist in many different sizes and shapes. Some of the smallest bacterial cells are short cylindrical objects less than 1 µm in length. At the other extreme, nerve cells have complex shapes including many long thin extensions, and may reach lengths of several metres (those in the neck of a giraffe provide a dramatic example). Between these extremes, plant cells are typically 20-30 µm long, polygon-shaped with box-like boundaries defined by rigid cell walls. Most cells in animal tissues are compact in shape, 10-20 µm in diameter with an irregular and often richly folded surface.

Plant Cell

Plant cells contain a variety of membrane-bound structures called organelles. These include a nucleus that carries genetic material; mitochondria that generate energy; ribosomes and rough endoplasmic reticulum that manufacture proteins; smooth endoplasmic reticulum that manufactures lipids used for making membranes and storing energy; and a thin lipid membrane that surrounds the cell. Plant cells also contain chloroplasts that capture energy from sunlight and a single fluid-filled vacuole that stores compounds and helps in plant growth. Plant cells are surrounded by a rigid cell wall that protects the cell and maintains its shape.

 

Despite their many differences in appearance and function, all cells have a surrounding membrane (termed the plasma membrane) enclosing a water-rich substance called the cytoplasm. All cells carry out multiple chemical reactions that enable them to grow, produce energy, and eliminate waste, together termed metabolism (from a Greek word meaning “change”). All cells contain hereditary information, packed into a central nucleus and encoded in molecules of deoxyribonucleic acid (DNA), which directs the cell's activities and enables it to reproduce, passing on its characteristics to its offspring. These and other similarities too numerous to mention, and including many identical or nearly identical molecules, demonstrate that all modern cells are related to one another. In other words, there must have been an unbroken continuity between modern cells—and the organisms they compose—and the first primitive cells that appeared on Earth.

A   The Chemistry of Cells

 

There is nothing in living organisms, or the cells from which they are made, that contravenes chemical and physical laws. However, the chemistry of life is based overwhelmingly on carbon compounds and depends almost exclusively on chemical reactions that take place in aqueous solution and in the relatively narrow range of temperatures experienced on Earth. The chemistry of living organisms is also very much more complicated than any other chemical system known. It is dominated and coordinated by enormous polymeric molecules (macromolecules) made from chains of linked chemical subunits. The unique properties of macromolecules endow cells with all of the properties we recognize as living, such as the ability to grow, to move, to reproduce, and to respond in an informed way to changes in their environment.

DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) (see Nucleic Acids) are the information-carrying macromolecules that encode the complex form and composition of an organism and allow it to be perpetuated from one generation to another. Unique among molecules, they provide directions for their own replication, thereby providing a basis for the continuity of life. DNA molecules are extremely long polymers made from four nucleotide bases —adenine, cytosine, guanine, and thymine—often represented by the letters A, C, G, and T, in a linear sequence. A typical chromosome in a human cell, for example, consists of two strands of DNA, each of which might contain 50 million to 100 million bases in a unique and precisely determined sequence. The cell has 46 chromosomes of this kind and the same set of chromosomes, each with an essentially identical base sequence, can be found in every one of the other hundreds of millions of cells in the body. One of the most exciting developments in recent years has been the elucidation of the complete sequence of nucleotides in the DNA of many organisms, including humans (see Human Genome Project).

RNA molecules are built to a similar plan as DNA, but they are much shorter and slightly different chemically; their four bases are adenine, cytosine, guanine, and uracil rather than thymine (represented by A, C, G, and U, not T). RNA molecules are made as copies of selected regions for the DNA, usually for the purpose of making protein.

If we liken DNA to the program, or software, of the cell, then proteins are its hardware: the physical bricks from which the cell is built. Protein molecules perform a bewildering variety of functions. As well as providing building blocks, proteins also act as enzymes to catalyse the myriad reactions inside a cell. Proteins embedded in the plasma membrane form channels and pumps that control the passage of small molecules into and out of the cell. Some proteins carry messages from one cell to another while others act as signal integrators that relay sets of signals from the plasma membrane to the nucleus of individual cells. Yet others serve as tiny molecular machines with moving parts that propel organelles through the cytoplasm or untangle knotted DNA molecules. Highly specialized proteins act as antibodies, toxins, hormones, antifreeze molecules, elastic fibres, ropes, or sources of bioluminescence.

In chemical terms, proteins are long linear polymers of amino acids joined head to tail by peptide bonds. In contrast to DNA and RNA, which are made of nucleotide subunits that are chemically very similar to each other, proteins are built up from an assortment of 20 amino acids that differ greatly in their chemical “personalities”. Each chain of amino acids folds into a particular shape, or conformation, in which some amino acids are buried on the inside, and other are exposed to the surrounding water. It is the chemistry of amino acids on a protein surface that specify its interactions with other molecules and determine its function, as an enzyme, or structural protein, or whatever. The sequence of amino acids in a protein, on which its properties depend, is itself specified by the sequence of nucleotide bases in one particular region of the DNA. A complicated machinery inside the cell first copies this region of DNA into a smaller RNA molecule, and then uses this RNA to direct amino acids to the machinery that links them together, in the correct sequence.

B   Prokaryotes and Eukaryotes

 

A fundamental division, both in size and in internal organization, exists between prokaryotic cells and eukaryotic cells. Prokaryotic cells, found only in bacteria and cyanobacteria (formerly known as blue-green algae), are relatively small (1-5 µm in diameter) and simple; their genetic material (DNA) is concentrated in one region of the cytoplasm but no membrane separates this region from the rest of the cell. Eukaryotic cells, from which all other living organisms are made, including protozoa, plants, fungi, and animals, are much larger (typically 10-30 µm in linear dimension) and their genetic material is enclosed by membrane, forming a conspicuous spherical body termed a nucleus. In fact, the name 'eukaryotic' comes from Greek words meaning 'true kernel, or nucleus'; 'prokaryotic' means 'before nucleus'.

C   Cell Surface

 

A thin oily skin termed the plasma membrane encloses the contents of all living cells, defining the boundary between the contents of the cytoplasm and the surroundings. The plasma membrane is a continuous layer of lipid and protein molecules about 5 nanometres (nm) thick that acts as a selective barrier to regulate the cell's chemical composition. When lipid molecules such as phospholipids and cholesterol are mixed with water they spontaneously form thin sheets, or bilayers, that close up into vesicles. Water-soluble ions and molecules are unable to cross a bilayer unaided, but can cross if specific carrier proteins or channels made of protein are embedded in the lipid. In this way the cell is able to maintain concentrations of such ions and small molecules that are different from those of their surroundings. A different mechanism, involving small membrane vesicles that add to or bud from the plasma membrane, allows animal cells to secrete or uptake macromolecules and even particles the size of bacteria across their membranes.

Many other proteins are present in the plasma membrane, the actual mixture being a distinctive feature of a particular cell type. Membrane proteins can work as enzymes to catalyse specific reactions or serve to link the membrane to the matrix of proteins on the outside of the cell, or to the cytoskeleton on the inside. Still other membrane proteins function as receptors that detect substances such as growth factors in the cell’s environment and signal their presence to the cytoplasm or nucleus.

The cells of bacteria, yeasts, fungi, and plants usually have, in addition to a plasma membrane, a relatively thick and sturdy cell wall made of polysaccharides (predominantly cellulose in the case of higher plants). The cell wall, which is external to the plasma membrane, maintains the shape of the cell and protects it from mechanical damage, but it also restricts the movements of the cell and limits the entry and exit of materials.

Although animal cells lack a rigid cell wall, they often secrete a tough “exoskeleton” which can have a major influence on the form of the cell. In most tissue of the human body, for example, cells are enclosed in an extracellular matrix composed of tough fibrous proteins such as collagen and variable amounts of proteoglycans, made of proteins linked to long, highly charged polysaccharides. The extracellular matrix is especially abundant in connective tissues, where it forms the basis of bone and cartilage, but can also be found in endothelia, epithelia, nerve, and muscle.

D   The Nucleus

 

 

Nucleus of a Cell

The nucleus, present in eukaryotic cells, is a discrete structure containing chromosomes, the genetic blueprint of the cell. Separated from the cytoplasm of the cell by a double-layered membrane called the nuclear envelope, the nucleus contains a cellular material called nucleoplasm. Nuclear pores, around the circumference of the nuclear membrane, allow the exchange of cellular materials between the nucleoplasm and the cytoplasm.

 

The most conspicuous organelle in most plant and animal cells is the nucleus, typically a membrane-enclosed, roughly spherical body about 5 µm in diameter. Within the nucleus, molecules of DNA and proteins are organized into long chromosomes, which usually occur in identical pairs. Chromosomes are too stringy and intertwined to be identified separately unless the cell is dividing. Just before a cell divides, however, its chromosomes become condensed and thick enough to be seen as separate structures. The DNA inside each chromosome is a single very long, highly coiled molecule containing a linear sequence of genes. Genes contain the coded instructions for the assembly of RNA molecules and proteins needed to produce a functioning copy of the cell.

The nucleus is enclosed in a two-layered membrane and interaction between the nuclear contents and the cytoplasm is permitted through holes, called nuclear pores, in this membrane. A specialized region, the nucleolus, is the site of assembly of particles containing RNA and protein, which migrate through the nuclear pores to the cytoplasm and are modified to become ribosomes.

The nucleus controls protein synthesis in the cytoplasm by sending molecular messengers in the form of RNA. This messenger RNA (mRNA), as it is called, is made in the nucleus according to instructions in the DNA, after which mRNA conveys the messages to the cytoplasm via the nuclear pores. Once in the cytoplasm, the mRNA attaches to ribosomes and a genetic message is translated into the primary structure of a specific protein.

E   Cytoplasm and Cytosol

 

 

Cytoplasm

This freeze-fracture transmission electron micrograph of a yeast cell, Rhodosporidium toryloides, shows a number of organelles suspended in its cytoplasmic matrix: a dark, round lipid body occupies the bottom of the cell, with the large nucleus above and to the right, and a curved mitochondrion at the top of the cell. High-voltage magnification reveals that the cytoplasm, here a viscous gel, contains a three-dimensional lattice of protein fibres. Called the cytoskeleton, these filaments interconnect and support the “solid” substances mentioned above.

 

The entire volume of a cell, excluding the nucleus, is called its cytoplasm, which includes many specialized structures and organelles, as described below. The concentrated aqueous solution in which these organelles are suspended is termed the cytosol. This is a water-based gel containing a host of large and small molecules and in most cells it is by far the largest single compartment (in bacteria it is the only intracellular compartment). The cytosol is the site of many of the most important housekeeping functions of the cell, including the early stages of breakdown of food molecules and the synthesis of many of the large molecules from which a cell is built. Whereas many molecules in the cytosol exist in true solution, moving rapidly from one location to another by free diffusion, other molecules are more highly ordered. These ordered structures give the cytosol an internal organization that provides a framework for the manufacture and breakdown of large molecules, and they channel many of the chemical reactions of the cell along spatially restricted pathways.

F   Cytoskeleton

 

 

Cytoskeleton

A network of protein fibres criss-crosses the cytoplasm of eukaryotic cells, providing shape and mechanical support. The cytoskeleton also functions as a monorail to transport substances around the cell. A cell such as an amoeba changes shape by dismantling parts of the cytoskeleton and reassembling them in other locations.

 

The cytoskeleton is a cohesive meshwork of protein filaments extending throughout the cytoplasm of plant and animal cells. The cytoskeleton is the primary determinant of cell shape and movement and to this end it operates according to its own functional 'logic' or set of rules. From a mechanical standpoint, the cytoskeleton acts like a set of struts and girders that support the form of the cell, constraining movements according to engineering parameters, such as elasticity and bending modulus. From a biochemical standpoint, the cytoskeleton undergoes a repertoire of characteristic reactions that take place over and over again as living cells move. These reactions include the polarized growth and shrinkage of protein polymers, their association through multiple linking proteins into larger structures, and the directed motion of motor proteins walking along protein polymers.

In a typical animal cell, the peripheral region, just beneath the plasma membrane, consists largely of a dense three-dimensional meshwork of thin filaments. This mesh is composed of actin filaments (microfilaments), which are thin, flexible filaments with a diameter of about 8 nm made of the protein actin. Microfilaments are often cross-linked into a dense, three-dimensional weave and they can also be more regularly arranged into parallel bundles, such as those that form the core of filopodia on the cell surface. The cortical meshwork contains small amounts of other material, thought to represent soluble proteins of the cytoplasm, but relatively few membrane-bounded organelles. Large bundles of actin filaments are found in muscle cells where, together with the protein called myosin, they produce forceful contractions.

By contrast, the central region of most cells, close to the nucleus, has a more open construction with fewer actin filaments and a smaller number of long microtubules, interspersed by abundant granular material and membrane organelles, including mitochondria. Microtubules are long polymers of the protein tubulin that stand out because they are relatively thick and inflexible. In thin sections they are even more conspicuous because of their hollow cylindrical form: a microtubule has an outer diameter of 25 nm, and a central canal, or lumen, of about 15 nm diameter. Many cells possess flexible 'hairs' on their surface, called cilia or flagella, which contain a core bundle of microtubules capable of regular, energy-driven bending movements. Sperm cells swim by means of flagella, for example, and cells lining the intestine or other ducts in the vertebrate body carry fields of motile cilia on their surfaces that sweep fluids and particles in a specific direction.

A third category of protein filament, widely found in animal cells and often located in the central region together with microtubules, is intermediate filaments. Their distribution is often similar to that of the cell’s microtubules, but they can be distinguished from the latter by their smaller diameter (about 10 nm) and absence of a hollow lumen. Intermediate filaments terminate on the matrix of protein that encloses the nucleus and radiate from there into the surrounding cytoplasm, often impinging on membrane-associated junctions with neighbouring cells. They are irregular, flexible ropes, composed of a diverse family of proteins and their principal function appears to be to confer mechanical strength to living cells.

Cell movements in eukaryotic cells almost always depend on actin filaments or microtubules. In broad terms, they are produced by one of two mechanisms. In the first, arguably the most primitive, the cell produces movement by controlling the polymerization of actin filaments or microtubules at specific locations. For example, the nucleation and growth of actin filaments at one location of a cell drives its plasma membrane forward, causing the boundary of the cell to extend over a solid surface. Similarly, the controlled polymerization of microtubules in a nerve cell axon helps to elongate and support the growing axon. The second general mechanism of movement is driven by motor proteins, which utilize the energy in ATP to move stepwise along a protein polymer. For example, growth and survival of the nerve axons just mentioned depends on motor proteins called dynein and kinesin. These move along microtubules inside the nerve axon, ferrying proteins, vesicles and organelles from the cell body to the synapses or in the reverse direction. Eukaryotic cells also contain a variety of myosins, which are motor proteins that move along actin filaments. Myosins not only transport materials such as RNA molecules and organelles from one location to another, but also are responsible for contractions and other movements of different parts of the cell (the best-known example being that of muscle cell contraction).

G   Mitochondria and Chloroplasts

 

 

Mitochondria

Mitochondria, minute sausage-shaped structures found in the hyaloplasm (clear cytoplasm) of the cell, are responsible for energy production. Mitochondria contain enzymes that help to convert food material into adenosine triphosphate (ATP), which can be used directly by the cell as an energy source. Mitochondria tend to be concentrated near cellular structures that require large inputs of energy, such as the flagellum, which is responsible for movement in vertebrate sperm cells and single-celled plants and animals.

 

Mitochondria are among the most conspicuous organelles in the cytoplasm, and, like the nucleus, they are present in essentially all eukaryotic cells. They have a very distinctive structure when seen in the electron microscope: each mitochondrion is usually sausage-shaped, several micrometres long, and enclosed in two separate membranes, the inner one being highly folded. Mitochondria are energy-producing organelles. Cells need energy to grow and replicate and mitochondria supply most of this energy by performing the last stages of the breakdown of food molecules. These stages involve the consumption of oxygen and the production of carbon dioxide; the entire process is called respiration, because of its similarity to breathing. Without mitochondria, animals and fungi would be unable to use oxygen to extract the full amount of energy from the food they consume to fuel their growth and replication. Various organisms that live in environments that lack oxygen are said to be anaerobicand they all lack mitochondria.

Chloroplasts

An examination of leaves, stems, and other types of plant tissue reveals the presence of tiny green, spherical structures called chloroplasts, visible here in the cells of an onion root. Chloroplasts are essential to the process of photosynthesis, in which captured sunlight is combined with water and carbon dioxide in the presence of the chlorophyll molecule to produce oxygen and sugars that can be used by animals. Without the process of photosynthesis, the atmosphere would not contain enough oxygen to support animal life.

 

Chloroplasts are large green organelles that are found only in the cells of plants and algae but not in the cells of animals or fungi. They have an even more complex structure than mitochondria: in addition to the two surrounding membranes, they have multiple sacs in their interior formed from a membrane that contains the green pigment chlorophyll. From the standpoint of life on Earth, chloroplasts carry out an even more essential task than mitochondria: they perform photosynthesis—that is, they trap the energy of sunlight in chlorophyll molecules and use this energy to drive the manufacture of small, energy-rich, carbon-containing molecules. In the process they release oxygen. Thus chloroplasts generate both the food molecules and oxygen that mitochondria use.

H   Internal Membranes

 

 

Rough Endoplasmic Reticulum

The major site of protein synthesis within the cell is on the surface of the rough endoplasmic reticulum (RER). Characterized by a stacked, sheet-like appearance dotted with small dark structures called ribosomes, the RER synthesizes proteins on its outer surface, then secretes these proteins to the outside of the cell. The ribosomes dotting the surface of the RER are also sites of protein synthesis, however these proteins are retained within the cell to perform metabolic functions.

 

Nuclei, mitochondria, and chloroplasts are not the only membrane-bounded organelles inside eukaryotic cells. The cytoplasm also contains a complex profusion of other organelles, each enclosed by a single membrane, that perform many distinct functions. Most of these functions are concerned with the cells’ need to import raw materials and export manufactured substances and waste products. Thus organelles of one class are enormously enlarged in cells that are specialized for secretion of proteins; organelles of another class are especially plentiful in cells in higher vertebrates that capture and digest viruses and bacteria that have invaded the body.

Golgi Apparatus

The golgi apparatus, a minute cellular inclusion in the cytoplasm, is a series of smooth, stacked membranous sacs. The golgi apparatus directs newly synthesized proteins to the correct destination in the cell.

 

An irregular three-dimensional network of spaces enclosed by membrane, called the endoplasmic reticulum (ER), is the site at which most cell membrane components are made, as well as materials destined for export from the cell. Stacks of membrane-bounded flattened sacs constitute the Golgi apparatus, which receives the molecules made in the endoplasmic reticulum, processes them, and then directs them to various locations in the cell. Lysosomes are small, irregularly shaped organelles that contain stores of enzymes responsible for the digestion of many unwanted molecules in cells. Peroxisomes are small, membrane-bounded vesicles that provide a contained environment for reactions where dangerously reactive hydrogen peroxide is generated and degraded. Membranes form numerous other small vesicles of many different types involved in the transport of materials between one membrane-bounded organelle and another. In a typical animal cell the membrane-bounded organelles may occupy up to a half the total cell volume.

I   Secretion and Endocytosis

 

One of the most important functions of vesicles is to carry materials to and from the plasma membrane, thereby providing a means of communication between the interior of the cell and its surroundings. A continual exchange of materials takes place among the endoplasmic reticulum, the Golgi apparatus, the lysosomes, and the outside of the cell. The exchange is mediated by small membrane-bounded vesicles that pinch off from one membrane and fuse with another.

At the surface of the cell, portions of the plasma membrane continually bud inwards and pinch off to form vesicles. These carry material captured from the external medium to the cell interior—a process termed endocytosis. The reverse process, called secretion, which takes place when vesicles from inside the cell fuse with the plasma membrane and release their contents into the external medium, is also common in many cells.

Several kinds of endocytosis can be distinguished, the most dramatic being the ingestion of large particles such as bacteria and cell debris, called phagocytosis or “cell eating”. Carnivorous amoebae perform phagocytosis as a means of feeding, whereas certain types of cells in the human body, such as macrophages, defend us against infection by ingesting micro-organisms that have invaded the body. An even more widespread form of uptake is termed pinocytosis, or “cell drinking”. Most types of animal cells, for example, continually ingest fluid and bits of plasma membrane by means of small vesicles that bud inwards and are taken into the cytoplasm. The rate of uptake by pinocytosis can be surprisingly large, and some cells can ingest 10 per cent or more of their own volume every hour.

Finally, there is a much more selective kind of uptake that depends on the cell having specific types of receptors in its membrane. Receptor-mediated endocytosis provides a concentrating mechanism by which a cell can take up essential macromolecules from the surrounding fluid without having also to ingest a huge volume of fluid. This is the mechanism by which cholesterol, an essential component of membranes, is taken up from the bloodstream, and also the method of uptake of vitamin B12, iron, and other essential metabolites. Unfortunately, receptor-mediated endocytosis can also be exploited by viruses, and provides the route by which the influenza virus and HIV, which causes AIDS, gain entry into cells.

V   CELL GROWTH AND DIVISION

Mitosis

This interactivity outlines the stages involved in mitosis, the division of a cell to produce two identical cells.

 

Living cells reproduce by carrying out an orderly sequence of events in which they duplicate their contents and then divide into two. In unicellular organisms, such as bacteria and yeasts, each cell division produces a complete new organism, whereas many rounds of cell division are required to make a new multicellular plant or animal from a single-celled egg. Once a plant or animal has reached its fully mature state, then many of its cells cease to divide and remain in their differentiated state for the life of the organism. However, there are also cells that die and need to be replaced. In adult humans for example, liver cells divide once every year or so, whereas some of the epithelial cells lining the gut and many of the blood cell precursors in the bone marrow divide more than once every day. In fact, each of us must manufacture many millions of cells every second simply to survive.

Cell division is at its simplest and most rapid in bacteria, which do not have a nucleus and contain a single chromosome. In the common gut bacterium Escherichia coli, for example, the whole cell cycle can take as little as 20 minutes under favourable growth conditions. Its circular chromosome, containing a single DNA molecule, is attached to the plasma membrane and remains attached while it replicates. The two new chromosomes then become separated as the cell grows. When the cell has approximately doubled in size, cell division occurs by simple fission as new cell wall and plasma membrane is laid down between the two chromosomes to produce two separate daughter cells.

Division in eukaryotic cells is significantly more complicated than in bacteria. The cells are many thousand times larger in volume and contain many organelles and other cytoplasmic structures, all of which have to be duplicated and then segregated into one of the two daughter cells. In particular, the DNA of eukaryotic cells is enormously long and requires an intricate intracellular apparatus for its maintenance and replication. For instance, all 46 chromosomes of a human tissue cell have to replicate individually and then physically move into one or another newly formed daughter cell. These elaborate rearrangements require many coordinated movements and major structural changes in the cytoskeleton.

The Cell Cycle

The cell cycle here shows the phases that a cell undergoes from the moment of its formation to its division into two daughter cells. It comprises interphase, when the cell is metabolically active, and mitosis, in which the cell gives rise to two daughter cells that are genetically identical to it and each other. The stages of mitosis are prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis.

 

 

Progression from one cell cycle stage to the next is controlled, as if by clockwork, by a series of biochemical reactions. These occur in a single direction and if necessary can be halted at critical steps, sometimes called checkpoints. One point of no return, for example, is when the nuclear membrane breaks down and the cell becomes committed to division of the nucleus, known as mitosis. A second irreversible step is the separation of chromosomes, which marks the exit from mitosis. This ability to arrest the cycle is crucial for the cell, since it allows division to respond to external conditions, such as the presence of growth factors. It is also necessary to synchronize nuclear events with cytoplasmic events, for example ensuring that mitosis does not begin before the DNA has been completely copied.

Summarizing a great deal of complicated biochemistry, it can be said that progression through the cell cycle is driven by the episodic synthesis and precipitous breakdown of small proteins, called cyclins. The cyclins activate specific protein kinases, called cyclin-dependent kinases, which phosphorylate many different target proteins and thereby control events such as DNA synthesis and entry into mitosis.

As it grows and divides, a eukaryotic cell passes through a number of stages, driven by the biochemical clockwork just mentioned. These are characterized by distinct events affecting both DNA and the cytoskeleton. The complete sequence of stages is referred to as the cell cycle, since it repeats over and over for as long as cell division continues. Division of the nucleus, or mitosis, is actually a relatively short episode in the cell cycle. It is preceded by a prolonged interphase, during which the cell duplicates its contents, both nuclear and cytoplasmic, and is closely followed by cytokinesis—the process by which the two newly produced cells are physically separated. Mitosis itself is traditionally subdivided into a sequence of stages according to the behaviour of the chromosomes as seen in the light microscope, the principal stages being prophase, metaphase, anaphase, and telophase.

Sperm and eggs are produced by a special kind of cell division called meiosis, in which the number of chromosomes is precisely halved. The actual process is complicated and entails first the duplication of chromosomes, then the association of maternal and paternal chromosomes to form “tetrads” (which allow the exchange of genetic material by chromosomal crossovers). Two successive divisions then produce the final haploid (that is, containing a single—not double—set of chromosomes) egg or sperm cell.