Chapter 3: Cells

Flagella

(meaning "whiplike") are similar to cilia in that both are hairlike projections of the cell membrane. Flagella, however, are thicker, longer, and fewer in number; they help move the cell. The tail of the sperm is an example of a flagellum; the tail enables the sperm to swim.

Microvilli

Accordion-like folds in the membrane; increase transport of water and dissolved solute

Cell Division

Cell division is necessary for the body's growth, repair, and reproduction. The frequency of cell division varies considerably from one tissue to the next. Some cells reproduce very frequently, whereas other cells reproduce very slowly or not at all. For example, the cells that line the digestive tract are replaced every few days, and more than 2 million RBCs are replaced every second. Certain nerve cells in the brain and spinal cord, however, do not reproduce at all. Two types of cell division are mitosis and meiosis. Meiosis occurs only in sex cells and will be discussed in Chapter 26. Mitosis, which is involved in bodily growth and repair, is the splitting of one mother cell into two identical "daughter cells." The key word is identical. In other words, an exact copy of genetic information, stored within the chromosomes, must be passed from the mother cell to the two daughter cells. Mitosis is described in more detail in the next section ("Cell Cycle").

Movement Across the Cell Membrane

Cells are bathed in an extracellular fluid that is rich in nutrients such as oxygen, glucose, and amino acids. These nutrients are needed in the cell and must therefore be able to cross the cell membrane. The cell's waste, which accumulates within the cell, must also be able to cross the cell membrane. Wastes are eventually eliminated from the body. A number of mechanisms assist in the movement of water and dissolved substances across the cell membrane. The transport mechanisms can be divided into two groups: passive transport and active transport mechanisms. Table 3.2 summarizes both types of transport. The passive transport mechanisms require no additional energy in the form of ATP. Passive transport is something like the downward movement of a ball (Fig. 3.6A). The ball is at the top of the hill. Once released, the ball rolls downhill. The ball does not need to be pushed; it moves passively, without any input of energy. Passive transport mechanisms cause water and dissolved substances to move without additional energy, like a ball rolling downhill. Active transport mechanisms require an input of energy in the form of ATP. Active transport is like the upward movement of a ball (see Fig. 3.6B). For the ball to move uphill, it must be pushed, therefore requiring an input of energy.

Cell Membrane

Contains the cellular contents; selects what enters and leaves the cell

Nucleus

Control center of the cell; stores genetic information

Diffusion

Diffusion is the most common transport mechanism. Diffusion is the movement of a substance from an area of higher concentration to an area of lower concentration. For example, a tablet of red dye is placed in a glass of water (Fig. 3.7A). The tablet dissolves, and the dye moves from an area where it is most concentrated (glass 1) to an area where it is less concentrated (glasses 2 and 3). Diffusion continues until the dye is evenly distributed throughout the glass. The point at which no further net diffusion occurs (glass 3) is called equilibrium. The scent of our pet skunk, Perfume, also illustrates diffusion (see Fig. 3.7B). Perfume's scent does not take long to permeate the area! Diffusion is involved in many physiological events. For example, diffusion causes oxygen to move across the membrane of an alveolus of the lung into the blood (see Fig. 3.7C). Oxygen diffuses from the alveolus because the concentration of oxygen is higher within the alveolus than within the blood. Conversely, carbon dioxide, a waste product that accumulates within the blood, diffuses in the opposite direction (carbon dioxide moves from the blood into the alveolus). The lungs then exhale the carbon dioxide, thereby eliminating waste from the body. Thus, the process of diffusion moves oxygen into the blood and carbon dioxide out of the blood.

Interphase

During interphase, the cell carries on with its normal functions and gets ready for mitosis through growth and DNA replication. Interphase is divided into three phases: first gap phase (G1), phase (S), and second gap phase (G2). • First gap phase (G1)—During this phase, the cell carries on its normal activities and begins to make the DNA and other substances necessary for cell division. • Phase S—During the S phase, the cell duplicates its chromosomes, thereby making enough DNA for two identical cells. • Second gap phase (G2)—This phase is the final preparatory phase for cell division (mitosis); it includes the synthesis of enzymes and other proteins needed for mitosis. At the end of G2, the cell enters the mitotic (M) phase.

Mitosis

During the mitotic (M) phase, the cell divides into two cells in such a way that the nuclei of both cells contain identical genetic information. Mitosis consists of four phases: prophase, metaphase, anaphase, and telophase (Fig. 3.14). • During prophase, the chromosomes coil so tightly that they become visible under a light microscope. Each chromosome pair is composed of two identical strands of DNA called chromatids; each chromatid is attached at a point called the centromere. At the same time, two pairs of centrioles move to opposite poles of the nucleus. Late in prophase, the nuclear membrane disappears. • During metaphase, the chromatids are aligned in a narrow central zone; spindle fibers connect the chromatids and centrioles. • Anaphase begins when the centromere splits and the chromatids are pulled to opposite poles (end of anaphase). • During telophase, each new cell reverts to the interphase state; the nuclear membrane reforms, the chromosomes uncoil, and the chromatin strands reappear. Telophase and cytokinesis mark the end of mitosis. Cytokinesis (sye-toh-kin-EE-sis), which begins in late anaphase, is the pinching of the cell membrane to split the cytoplasm into two distinct cells. Repeat! Mitosis is a type of cell division that produces two genetically identical daughter cells. How can you remember the stages of mitosis? Think of "Play Me A Tune": prophase, metaphase, anaphase, telophase. At the end of mitosis, the daughter cells have two choices. They can enter G1 and repeat the cycle (and divide again) or they can enter another phase, called G zero (G0) (see Fig. 3.13). Cells in G0 "drop out" of the cell cycle and rest; they do not undergo mitosis. Cells may re-enter the cell cycle after days, weeks, or years. The inability to stop cycling and enter G0 is characteristic of cancer cells. Cancer cells constantly divide and proliferate. Anticancer drugs are more active against cells that are cycling than against cells resting in G0. Thus, tumors that contain many cycling cells respond best to chemotherapy. Anticancer drugs are classified according to the cell cycle phases that they affect. Some anticancer drugs are called cell cycle phase-specific. These drugs affect the cell when it is in a particular phase. With the use of this terminology, the anticancer drug methotrexate is considered cell cycle S phase-specific. Other drugs are cell cycle M phase-specific and cell cycle G2 phase-specific. Some anticancer drugs can act at any phase of the cell cycle and are called cell cycle phase-nonspecific. By knowing the cell cycle terminology, you can understand anticancer drugs better.

Facilitated Diffusion

Facilitated diffusion is a form of diffusion that is responsible for the transport of many substances (facilitate means "to help"). As in diffusion, substances move from a higher concentration toward a lower concentration (Fig. 3.8). In facilitated diffusion, however, the substance is helped across the membrane by a molecule within the membrane. The helper molecule increases the rate of diffusion. The transport of glucose by facilitated diffusion is illustrated in Fig. 3.8 by a boy carrying the glucose. Note that he is moving downhill, indicating that facilitated diffusion is a passive transport process.

Microvilli

For cells that are particularly involved with the movement of large amounts of water and its dissolved solutes, the membrane forms accordion-like folds called microvilli (sing., microvillus). The folding of the cell membrane increases surface area, thereby increasing the amount of fluid absorbed. For example, some of the cells in the digestive tract have millions of foldings, called microvilli, to absorb water and the end products of digested food.

Nucleoplasm

Gel in the nucleus

Cytoplasm

Gel located inside the cell but outside the nucleus

Cilia

Hairlike projections that move substances across surface of cell membrane

Hypotonic Solution

If an RBC is placed in pure water (a solution containing no solute), then water moves into the cell by osmosis (from where there is more water to where there is less water). The pure water, being more dilute than the inside of the cell, is said to be hypotonic. Hypotonic solutions cause RBCs to burst, or lyse, in a process referred to as hemolysis. Because of hemolysis, pure water is not administered intravenously.

Hypertonic Solutions

If an RBC is placed within a very concentrated salt solution, water diffuses out of the RBC into the bathing solution, causing the RBC to shrink, or crenate. The salt solution is referred to as a hypertonic solution. Why is the tonicity of a solution important? If the cell gains water, the RBC membrane bursts. If the RBC loses water, the cell shrinks. In both cases, RBC function is impaired. Isotonic solutions do not cause cells to swell or shrink. While the RBC was used to explain tonicity, other cells respond in the same way. Clinically, isotonic solutions are frequently administered intravenously. Commonly used isotonic solutions include normal saline (0.9% NaCl), 5% D/W (5% dextrose or glucose in water, or D5W), and Ringer's solution. Under special conditions, hypotonic or hypertonic solutions may be administered intravenously.

Cytosol

Medium composed of water and dissolved solute; organelles suspended in the cytosol

Endoplasmic reticulum (ER)

Membranes that form channels for the flow of cellular substances such as proteins Rough ER... Contains ribosomes where protein is synthesized Smooth ER... Site of lipid and steroid synthesis; synthesis of glycogen in liver and skeletal muscle

On the Cell Membrane

Microvilli Cilia Flagella

Cytoplasmic Organelles

Mitochondria Ribosomes Endoplasmic Reticulum Golgi Apparatus Lysosomes Cytoskeleton Centrioles

Cell Differentiation

Mitosis assures us that the division of one cell produces two identical cells. How do we account for the differences in cells such as muscle cells, RBCs, and bone cells? In other words, how do cells differentiate or develop different characteristics? An embryo begins life as a single cell, the fertilized ovum. Through mitosis, the single cell divides many times into identical cells. Then, at some time during their development, the cells start to specialize, or differentiate (Fig. 3.15). One cell, for example, may switch on enzymes that produce RBCs. Other enzymes are switched on and produce bone cells. Regardless of the mechanism, you started life as a single adorable cell and ended up as billions of specialized cells! What does it mean when a tissue biopsy (surgical removal of tissue for examination) shows many poorly differentiated cells? It means that the tissue cells have failed to differentiate or specialize. In other words, the poorly differentiated cells of a liver tumor do not resemble normal liver cells. Failure to differentiate is characteristic of cancer cells.

Order, Disorder, and Death

Most cell growth is orderly. Cells normally reproduce at the proper rate and align themselves in the correct positions. At times, however, cell growth becomes uncontrolled and disorganized. Too many cells are produced. This process is experienced by the patient as a lump or tumor (tumor means "swelling"). Tumors may be classified as benign (noncancerous) or malignant (cancerous). Cancer cells are appropriately named. Cancer means "crab"; cancer cells, like a crab, send out clawlike extensions that invade surrounding tissue. Cancer cells also detach from the original tumor (primary site) and spread throughout the body (secondary sites). Widespread invasion of the body by cancer cells often causes death. The spreading of cancer cells is referred to as metastasis. There is also a programmed sequence of events that leads to cell death called apoptosis, or cell suicide. Apoptosis helps rid the body of old, unnecessary, and unhealthy cells. Because the body replaces a million cells per second, the elimination of some cells by apoptosis is necessary. Apoptosis, however, can go into overdrive, causing excessive cellular death and disease. A Pap smear is a diagnostic procedure used to detect cancer. A sample of cells (a smear) is obtained, usually from around the cervix. The smear is then examined under a microscope for changes that could indicate cancer. A positive Pap smear can indicate cancer in its early stages. Early detection is associated with a very high cure rate. Sometimes cells are injured so severely that they die, or necrose (from the Greek word necros, meaning "death"). For example, the cells may be deprived of oxygen for too long a period, be poisoned, be damaged by bacterial toxins, or suffer the damaging effects of radiation.

Nuclear membrane

Separates the nucleoplasm from the cytoplasm

Flagellum

Single long hair for swimming movement of the sperm

Mitochondria

Site of ATP production; "power plants" of the cell

Nucleolus

Synthesizes RNA and ribosomes

Cell Membrane

The cell is encased by a cell membrane, also called the plasma membrane. The cell membrane separates intracellular (inside the cell) material from extracellular (outside the cell) material. In addition to physically holding the cell together, the cell membrane performs other important functions. One of its chief functions is the selection of substances allowed to enter or leave the cell. Because the membrane chooses the substances allowed to cross it, the membrane is said to be selectively permeable, or semipermeable. What makes up a cell membrane? The cell membrane is composed primarily of phospholipids and protein, as well as a small amount of carbohydrates (Fig. 3.3). The phospholipids are arranged in two layers. The protein molecules in the membrane perform several important functions; they provide structural support for the membrane, act as binding sites for hormones, and poke holes, or pores, through the lipid membrane. These pores form channels through which water and dissolved substances flow. Substances move across the semipermeable membrane in two ways. They can dissolve in the lipid portion of the membrane, as do oxygen and carbon dioxide (lipid-soluble substances). Substances can also cross the membrane by flowing through the pores. Water and electrically charged substances such as sodium and chloride cannot penetrate the lipid membrane and must use the pores. These are called water-soluble substances. The size of the pores also helps select which substances cross the membrane. Substances larger than the pores cannot cross the membrane, whereas smaller substances such as sodium and chloride flow through easily. The solubility characteristics of the membrane also play an important role in pharmacology. Drugs are classified as lipid (fat) soluble or water soluble. Drug solubility determines its distribution throughout the body

Cytoplasm

The cytoplasm, or the "gel in the cell," is found inside the cell but outside the nucleus (like the white of a raw egg). The cytoplasm contains the cytosol and organelles. The cytosol is the intracellular fluid and is composed primarily of water, electrolytes, proteins, and nutrients. The cytosol also contains inclusion bodies, insoluble materials such as glycogen granules and pigments such as melanin. The organelles, or "little organs," are dispersed throughout the cytoplasm; each organelle has a specific role.

The endoplasmic reticulum

The endoplasmic reticulum (ER) is a network of membranes within the cytoplasm (see Fig. 3.2). These long, folded membranes form channels through which substances, especially newly synthesized protein, move. The two types of ER include the type containing ribosomes along its surface; it is called rough endoplasmic reticulum (RER) because of its rough, sandpaper-like appearance. The RER is primarily concerned with protein synthesis. Protein synthesized along the RER is transported through the channels and delivered to the Golgi apparatus for further processing. The ER that does not contain ribosomes on its surface appears smooth; it is called smooth endoplasmic reticulum (SER). SER is primarily involved in the synthesis of lipids, steroids, glycerides, and glycogen in skeletal muscle and liver cells.

Inside the Cell

The inside of the cell is divided into two compartments: the nucleus and the cytoplasm. The inside of the cell resembles the inside of a raw egg; the "yellow yolk" is the nucleus, and the "white" is the cytoplasm.

Mitochondria

The mitochondria are tiny, slipper-shaped organelles. The number of mitochondria per cell varies, depending on the metabolic activity of the cell (how hard the cell works). The more metabolically active the cell, the greater the number of mitochondria. The liver, for example, is very active and therefore has many mitochondria per cell. Bone cells are less active metabolically and have fewer mitochondria. The mitochondrial membrane has two layers (Fig. 3.4); the outer layer is smooth, whereas the inner layer has many folds, referred to as cristae. The enzymes associated with ATP production are located along the cristae. Because the mitochondria produce most of the energy (ATP) in the body, they are referred to as the "power plants" of the cell. (See Chapter 2 for an explanation of ATP and Chapter 4 for a description of ATP production.)

Nucleus

The nucleus is the control center of the cell (see Fig. 3.2). In particular, the nucleus contains the genetic information and controls all protein synthesis. Most adult cells have one nucleus; only mature RBCs have no nucleus. Surrounding the nucleus is a double-layered nuclear membrane. The nuclear membrane contains large pores that allow the free movement of certain substances between the nucleus and cytoplasm. The nucleus is filled with a fluid substance called nucleoplasm. Within the nucleoplasm are two other structures: the nucleolus and chromatin. The nucleolus, or little nucleus, synthesizes ribosomes that move through nuclear pores into the cytoplasm, where they play a role in protein synthesis. The nucleolus also produces a nucleotide necessary for protein synthesis. Chromatin is composed mainly of strands of DNA (deoxyribonucleic acid), the carriers of the genetic code. In nondividing cells, chromatin appears as a tangled array of fine filaments. In dividing cells, however, chromatin strands coil tightly, forming DNA-containing structures called chromosomes.

Chromatin

Threadlike structures in the nondividing cell that contain DNA; chromatin threads form chromosomes in a dividing cell

Organelles

Tiny organs suspended in the cytosol

Filtration

With diffusion and osmosis, water and dissolved substances move across the membrane in response to a difference in concentrations. With filtration, water and dissolved substances cross the membrane in response to differences in pressures. In other words, pressure pushes substances across the membrane. A syringe can illustrate filtration (Fig. 3.11). Syringe 1 is filled with water. If a force is applied to the plunger, the water is pushed out through the needle. The water moves in response to a pressure difference, with greater pressure at the plunger than at the tip of the needle. In the second syringe, tiny holes are made in the sides of the barrel. When force is applied to the plunger, water squirts out the sides of the syringe and out the tip of the needle. Where does filtration occur in the body? The movement of fluid across the capillary wall can be compared with the movement of water in the syringe with holes in its side (syringe 2). A capillary is a tiny vessel that contains blood. The capillary wall is composed of a thin layer of cells with many little pores. The pressure in the capillary pushes water and dissolved substances out of the blood and through the pores in the capillary wall into the tissue spaces. This process is filtration; it is movement caused by pushing.

Ribosomes

are cytoplasmic organelles involved in protein synthesis. Some ribosomes are attached to the endoplasmic reticulum and are called fixed ribosomes. Fixed ribosomes are largely concerned with the synthesis of exportable protein—that is, protein secreted by the cell for use elsewhere in the body. Other ribosomes, called free ribosomes, float freely within the cytoplasm and generally synthesize proteins that are used within the cell.

Lysosomes

are membranous sacs containing powerful enzymes. Lysosomal enzymes break down intracellular waste and debris, including damaged organelles, and thus help "clean house." Lysosomal enzymes perform several other functions. They participate in the destruction of ingested bacteria, a process called phagocytosis. Lysosomes also break down the contractile proteins of inactive muscles, as occurs in retired athletes and chronically bedridden persons.

Centrioles

are paired, rod-shaped, and short microtubular structures that form the spindle apparatus in a dividing cell. Cells that have no centrioles are incapable of cell division; these include neurons, mature RBCs, skeletal muscle cells, and cardiac muscle cells. The cytoplasm surrounding the centrioles is called the centrosome. Microtubules of the cytoskeleton begin at the centrosome and spread throughout the cytoplasm.

Stem cells

are relatively undifferentiated or unspecialized cells whose only function is the production of additional unspecialized cells. Each time a stem cell divides, one of its daughter cells differentiates while the other daughter cell prepares for further stem cell division. The rate of stem cell division varies with the tissue type; the stem cells within the bone marrow and skin are capable of dividing more than once a day, whereas the stem cells in adult cartilage may remain inactive for years. Stem cell research is of particular interest because of the possibility of replacing damaged tissue and growing new organs. How amazing it would be if newly discovered stem cells could be used to repair a damaged spinal cord or restore the dopamine-secreting cells in the brains of persons with Parkinson's disease. Another advance in stem cell research is the development of a new technique that coaxes adult cells to regress to an embryonic state. These undifferentiated cells are called induced pluripotent stem cells (iPS cells). The iPS cells can then be induced to specialize into the desired cell type, such as bone, muscle, or blood cells. A major hurdle in stem cell research has been the use of embryos as stem cell donors. This technique required the destruction of the embryo, thereby creating an ethical dilemma for many. The development of iPS cells eliminates this issue and hopefully will hasten stem cell research.

Cilia

are short, hairlike projections on the outer surface of the cell membrane. Cilia use wavelike motions to move substances across the surface of the cell. For example, cilia are abundant on the cells that line the respiratory passages. The cilia help move mucus and trapped dust and dirt toward the throat, away from the lungs. Once in the throat, the mucus can be removed by coughing or swallowing. The cilia therefore help clear the respiratory passages. Cigarette smoking damages the cilia and thus deprives the smoker of this benefit.

Isotonic Solution

has the same concentration as intracellular fluid (iso means "same"). Consider an RBC placed in an isotonic solution. Because the solution is isotonic, no net movement of water occurs; the cell neither gains nor loses water.

Active Transport Mechanisms

include active transport pumps, endocytosis, and exocytosis.

The Golgi apparatus

is a series of flattened membranous sacs (Fig. 3.5). Proteins synthesized along the RER are transported to the Golgi apparatus through channels formed by the ER. The Golgi apparatus puts the finishing touches on the protein. For example, a glucose molecule may be attached to a protein within the Golgi apparatus. A segment of the Golgi membrane then wraps itself around the protein and pinches itself off to form a secretory vesicle. In this way, the Golgi apparatus packages the protein. Note that many of the organelles, particularly the ribosomes, ER, and Golgi apparatus, are involved in protein synthesis. <garbage>

Osmosis

is a special case of diffusion. Osmosis is the diffusion of water through a selectively permeable membrane. A selectively permeable—or semipermeable—membrane allows the passage of some substances while restricting the passage of others. During osmosis, the water diffuses from an area with more water to one with less. The dissolved substances, however, do not move. Two different solutions in the glass illustrate osmosis. The glass is divided into two compartments (A and B) by a semipermeable membrane (Fig. 3.9). Compartment A contains a dilute glucose solution, whereas compartment B contains a more concentrated glucose solution. The membrane is permeable only to water. The glucose cannot cross the membrane and is therefore confined to its compartment. During osmosis, the water moves from compartment A to compartment B (from the area where there is more water to the area with less). The following two effects occur: (1) the amount, or volume, of water in compartment B becomes greater than the volume in compartment A; and (2) the concentrations of the solutions in both compartments change. The solution in compartment A becomes more concentrated, whereas the solution in compartment B becomes more dilute. Because water moves toward the more concentrated solution, it appears to be "pulled" in that direction. Sometimes osmosis is described as a "pulling" pressure. For example, Na+ is said to pull or hold water. More correctly stated, water diffuses into the more concentrated saline solution. Because osmosis causes water to move into a compartment, it can cause swelling. For example, tissue injury causes leakage and accumulation of proteins within the tissue space. The confined proteins act osmotically. Water diffuses toward the protein, causing the tissues to swell, a condition called edema.

Endocytosis

is a transport mechanism that involves the intake of food or liquid by the cell membrane (see Fig. 3.12B). In endocytosis, the particle is too large to move across the membrane by diffusion. Instead, the particle is surrounded by the cell membrane, which engulfs it and takes it into the cell. There are two forms of endocytosis. If the endocytosis involves a solid particle, it is called phagocytosis (fag-oh-sye-TOH-sis) (phago- means "eating"). For example, white blood cells eat, or phagocytose, bacteria, thereby helping the body defend itself against infection. If the cell ingests a water droplet, the endocytosis is called pinocytosis (pin-oh-sye-TOH-sis), or "cellular drinking."

Cytoskeleton

is composed of threadlike structures called microfilaments and microtubules. The cytoskeleton helps maintain the shape of the cell and assists the cell in various forms of cellular movement. Cellular movement is particularly evident in muscle cells, which contain large numbers of microfilaments. Microtubules are the primary component of the cytoskeleton. In addition to making the cell strong and rigid, the microtubules anchor the position of the organelles within the cytoplasm. Microtubules also play a key role in cell division; they form the spindle apparatus that helps distribute the chromosomes to opposite ends of the dividing cell.

Tonicity

is the ability of a solution to affect the volume and pressure within a cell. Note what happens when a cell is placed in solutions of different concentrations (Fig. 3.10). The following three terms are used to illustrate tonicity: isotonic, hypotonic, and hypertonic.

Cell Cycle

is the sequence of events that the cell goes through from one mitotic division to the next. The cell cycle is divided into two major phases: interphase and mitosis

Exocytosis

moves substances out of the cells (see Fig. 3.12C). For example, the cells of the pancreas make proteins for use outside the pancreas. The pancreatic cells synthesize the protein and wrap it in a membrane. This membrane-bound vesicle moves toward and fuses with the cell membrane. The protein is then expelled from the vesicle into the surrounding space.

Active Transport Pumps

refers to a transport mechanism that requires an input of energy (ATP) to achieve its goal. It is necessary to pump certain substances because the amount of some substances in the cell is already so great that the only way to move additional substances into the cell is to pump them in. For example, the cell normally contains a large amount of potassium ions (K+). The only way to move additional K+ into the cell is to pump it in. To move the K+ from an area of low concentration to an area of high concentration (uphill), energy is invested

Passive Transport Mechanisms

that move substances across the membrane include diffusion, facilitated diffusion, osmosis, and filtration.

Cells

the structural and functional unit of all living matter. Vary considerably in size, shape, and function (this is what reflects their specialized functions). A red blood cell (RBC), for example, is tiny, whereas a single nerve cell may measure 4 feet in length. The shapes and structures of the cells are also very different. The RBC is shaped like a Frisbee and is able to bend. The shape allows it to squeeze through tiny blood vessels and deliver oxygen and other nutrients throughout the body.