CellCHAPTER 1
INTRODUCTION
Cell is the structural, functional and developmental unit of life. The term cell was coined by the British scientist Robert Hooke in 1665. There are about 100 trillion cells in the human body, the most abundant being red blood corpuscles (25 trillion). Cell biology is the study of cellular structure and functions.
STRUCTURE OF A CELL
An animal cell consists of a cell membrane or plasma membrane which encloses cytoplasm and nucleus. The cell membrane is very thin and can be seen under an electron microscope. Detailed structure of the cell is shown in (Fig. 1.1).
Plasma Membrane
Each cell is enclosed by a membrane called plasma membrane which separates intracellular fluid from extracellular fluid. It protects the nucleus and the organelles. It is a selectively permeable membrane which regulates transport of substances into and out of the cell. It allows some substances to pass through it and excludes others. The nucleus and other organelles are also surrounded by a membrane.
Under electron microscope, the plasma membrane is a three-layered structure, 8-10 nm in thickness. Phospholipids, cholesterol and glycolipids form the major lipids of the cell membrane. Phospholipids are phosphatidylcholine and phosphatidylethanolamine. The shape of the phospholipid molecule is roughly that of a clothespin. The head end of the molecule contains a phosphate portion and is relatively soluble in water and is called polar or hydrophilic end. The tail portion is relatively insoluble and is called nonpolar or hydrophobic end. The uncharged hydrophobic end resides within the depth of the cell membrane and the charged hydrophilic end is exposed to the ECF and cytoplasm (Fig. 1.2).
The proteins associated with cell membrane are of two types: Integral proteins or transmembrane proteins span the whole width of the membrane and peripheral proteins are present on the surface of the cell membrane either on the inside or on the outside. Transmembrane proteins act as ion channels.
Functions of Cell Membrane Proteins
- Integral proteins contribute to the structure of cell membrane.
- Some cell membrane proteins anchor cells to their neighbors or to the basal lamina.
- Some proteins function as pumps for active transport of substances, e.g. Na+-K+ pump.
- Carrier proteins transport substances down their electrochemical gradient, e.g. glucose transporters (GLUT).
- Ion channels permit passage of ions into or out of the cell when activated e.g. Na+ channel, Ca2+ channel, etc.
- Some membrane proteins act as receptor sites for hormones and neurotransmitters, e.g. acetyl-choline (ACh) receptor, insulin receptor, etc.
- Some proteins act as antigens and stimulate antibody production.
CYTOPLASM
Cytoplasm consists of all the contents of cell between plasma membrane and nucleus. It is divided into cytosol and organelles. Cytosol is the fluid portion of cytoplasm containing water, proteins, lipids, solutes, etc. Organelles have characteristic shape and perform specific functions, e.g. centrosome, ribosome, endoplasmic reticulum, Golgi complex, lysosomes, peroxisomes, mitochondria, etc. (Fig. 1.1). Some organelles are bound by a limiting membrane and others do not have a limiting membrane. Ribosomes and cytoskeleton do not have limiting membrane.
Centrosome
Centrosome consists of a pair of centrioles. The centrioles are cylindrical structures, and each is composed of nine clusters of three microtubules arranged in a circular pattern. When a cell divides, the centrosomes duplicate themselves and the pairs move apart to form the poles of the mitotic spindles, which are made of microtubules.
Ribosomes
Ribosomes are small granular structures which contain ribosomal RNA (rRNA) and proteins. rRNA is synthesized by DNA in the nucleolus. Ribosomes are the site of protein synthesis in the cell. Ribosomes are of two types, free ribosomes present in the cytoplasm and bound ribosomes located in the rough endoplasmic reticulum. Bound ribosomes synthesize most of the proteins that are secreted by the cell.
Endoplasmic Reticulum
Endoplasmic reticulum is made up of tubules and vesicles. Endoplasmic reticulum is continuous with the nuclear membrane. Two types of endoplasmic reticulum are rough endoplasmic reticulum (RER) studded with ribosomes and smooth endoplasmic reticulum (SER), which has no ribosomes attached to it. RER synthesizes proteins. SER is the site of synthesis of fatty acids, phospholipids, steroids, etc. Steroid secreting cells are rich in SER. In skeletal and cardiac muscle cells, SER is called sarcoplasmic reticulum from which Ca2+ is released during muscle contraction. SER is also the site of detoxification of drugs and poisons especially in liver cells.
Golgi apparatus
Golgi apparatus is an organelle with secretory activity. It is present in all cells except red blood cells. It consists of flattened sacs called cisterns. Associated with cisterns are Golgi vesicles. The Golgi complex processes and delivers proteins and lipids to different parts of the cell. It also forms lysosome and secretory vesicles. The secretory vesicles bud off from the cistern into the cytoplasm and are finally exocytosed to the cell exterior.4
Lysosomes
Lysosomes are membrane-enclosed vesicles filled with enzymes which are budded off from the Golgi complex. It forms the digestive apparatus of the cell. Lysosomal enzymes are synthesized in the rough endoplasmic reticulum and then processed by the Golgi apparatus.
Functions
- There are about 40 different types of hydrolytic enzymes inside the lysosomes. They digest large molecules of proteins, polysaccharides, fats and nucleic acids.
- Lysosomes remove old and worn out cell organelles.
- Lysosomal enzymes released at the site of inflammation help to digest cellular debris, bacteria, etc. and prepare the area for repair.
- The granules of neutrophils, eosinophils and basophils are actually lysosomes.
Peroxisomes
Peroxisomes are structurally similar to lysosomes, but they are functionally different. They are much smaller in size. They remove the highly toxic hydrogen peroxide formed in the cell and thus protect the cell. Peroxisomes in the liver detoxify alcohol and other harmful compounds.
Mitochondria
Mitochondrion is a rod shaped structure with a diameter of 0.5 to 1μm. Mitochondria are called the powerhouses of the cell and are the sites of generation of ATP. It is covered by a double-layered membrane; the outer layer is smooth and the inner membrane is arranged in a series of folds called cristae. The cavity of mitochondrion is filled with matrix. Chemical reactions of cellular respiration occur in the matrix and cristae, catalyzed by enzymes present in these areas. Mitochondria contain their own DNA and so can replicate and increase their number. Mitochondrial genes are inherited from the mother in contrast to nuclear genes which are inherited from both parents.
Proteasomes
Lysosomes degrade proteins delivered to them in vesicles which are phagocytosed from outside. Sometimes the proteins formed in the cytoplasm also need to be removed from the cell. Proteasomes are tiny structures in the cell that cause continuous destruction of abnormal proteins and unneeded proteins produced inside the cell.
Cytoskeleton
Cytoskeleton is a network of different kinds of protein filaments present in the cytosol. It provides a structural framework for the cell. It also helps in the movement of organelles in the cell, movement of chromosomes during cell division and also helps in phagocytic activity. Three types of filaments contribute to cytoskeleton:
- Microfilaments
- Intermediate filaments
Microfilaments
Microfilaments are the thinnest elements which are about 3-5 nm in diameter. They are composed of two actin strands that are coiled helically. It provides mechanical support and helps in the movement of the cell. Microfilaments help in muscle contraction, cell division, movement of phagocytes to the sites of inflammation, etc. Microfilaments also support microvilli of epithelial cells.
Intermediate Filaments
Intermediate filaments are thicker than microfilaments with a diameter of 8-10 nm. They are made up of fibrous proteins. They help to maintain the shape of the cell. They help to stabilize the position of organelles like nucleus.
Microtubules
Microtubule is the largest cytoskeletal component. They are unbranched hollow tubular structures composed of the protein, tubulin (α-tubulin and β-tubulin subunits). Centrosome is the site of formation of microtubules. Functions of microtubules are:
- They help to maintain cell shape and also help in the movement of secretory vesicles and mitochondria from one part of the cell to another.
- They form mitotic spindle and participate in the movement of chromosomes during cell division.
- They also help in the movement of cilia and flagella.
Cilia and Flagella
Cilia and flagella are motile processes of cells. Both have the same diameter but flagella are about 10 times longer. Cilia usually occur in large numbers on cell surface while flagella are usually limited to one or two per cell. Mucociliary transport seen in respiratory tract is a function of cilia. Movement of sperm is due to flagellar action.
NUCLEUS
Nucleus is present in almost all cells of the body except some cells like mature red blood cells. The functions of nucleus are control of cellular activity and production of ribosomes in the nucleolus. Usually, one nucleus is present in each cell but there are exceptions. Skeletal muscle cells have more than one nucleus. Nucleus consists mainly of the chromosomes.
A double layered membrane called nuclear membrane separates nucleus from cytoplasm. The outer membrane is continuous with rough endoplasmic reticulum. Nuclear pores are openings present in the nuclear envelope which control movement of substances across nuclear membrane (Fig. 1.1).
The nucleus contains one or more nucleoli whose function is to produce ribosomes. It contains the genes for ribosome synthesis. Nucleolus is not enclosed by a membrane and contains protein, DNA and RNA. It is the site of synthesis of rRNA. Nucleoli disappear during cell division.
Each human cell except gametes, contain 23 pairs of chromosomes. In a pair, one chromosome is contributed by the mother and the other by the father and they are called homologous chromosomes. Each chromosome is made up of long DNA molecule coiled together in the form of a double helix to 6which several proteins are incorporated. This complex of DNA, proteins, especially histones and RNA forms chromatin.
Chromatin is made up of bead-like structures called nucleosome, which consists of double-stranded DNA wrapped around a core of 8 proteins called histones which help in the coiling and folding of DNA. Just before cell division, the DNA replicates and the loops condense to form a pair of chromatids which constitute a chromosome.
CELL DIVISION
A multicellular organism begins its life as a single cell formed by the fusion of ovum and sperm. This cell by the process of cell division and differentiation transforms into the multicellular organism. Cell division and differentiation continues till the death of the organism. Cell division are of two types:
- Mitosis occurring in somatic cells necessary for growth and repair
- Meiosis occurring in the germ cells of the gonads involved in sexual reproduction
Somatic Cell Division or Mitosis
In mitosis, a parent cell divides to produce two identical daughter cells with the genetic constitution same as that of the parent cell, i.e. the daughter cells contain same number of chromosomes as that of the parent cell. The daughter cells will be morphologically and physiologically similar.
Cell Cycle
Cell cycle includes the growth and division of a single cell into two daughter cells. A cell normally divides after a certain period of its growth. The cell division takes place when the cell has grown to its maximum size. Each cell has two phases in its life cycle:
- Interphase
- Cell division or mitotic phase
Interphase
The stage of a cell in between divisions is called interphase. During this stage, replication of DNA, centrosome and centrioles occur and the cell grows and prepares for cell division. The RNA and proteins necessary for the doubling of all cellular components are manufactured in this phase. The chromosomes are not visible in this phase. Interphase is divided into three phases:
- G1 phase (gap or growth phase) and G0 phase
- S phase (synthesis phase)
- G2 phase
G1 and G0 Phase
This phase occurs immediately after a cell division. Growth of the cell, metabolism and production of substances necessary for cell division occur in this phase. The duration of this phase varies in different situations. It is less in rapidly dividing cells like cells of bone marrow, germinal layers of skin, epithelium of gut, etc.
Cells that do not divide are permanently arrested in the G1 phase and is termed G0 phase. Neurons, heart muscle cells and skeletal muscle cells are in the G0 phase, i.e. they do not divide because they are permanently arrested in the G0 phase after birth.7
S Phase or Synthesis Phase
Chromosomes and centrosome replicate in this phase which is the longest phase. The original DNA molecule becomes 2 DNA molecules. Once a cell enters S phase, it is committed to undergo cell division.
G2 Phase
G2 phase is another period of growth of the cell. Centriole divides to form a new pair.
Mitotic Phase or M Phase
The cell division occurring in somatic cell is called mitosis. The daughter cells produced are quantitatively similar. This phase consists of two stages (Fig. 1.3):
- Nuclear division
- Cytoplasmic division
Nuclear Division
It consists of the following stages:
- Prophase
- Metaphase
- Anaphase
- Telophase
Prophase: This is the longest phase. The chromatin fibers condense and shorten to form chromosome which consists of two chromatids. The constriction that holds the chromatids together is the centromere. In late prophase, centrosome form mitotic spindle that gets attached to centromere. The centrosomes are pushed to the poles of the cell. The nucleolus disappears and nuclear membrane breaks down. The chromosomes now lie in the cytoplasm without any definite arrangement.
Metaphase: The chromosomes move towards the centre of the cell. The centromeres get arranged at the exact centre of the mitotic spindle and this part forms the equatorial plane. The chromosomes become visible in this stage.
Anaphase: This is the shortest phase. The centromeres split longitudinally and the two members of the chromatid pair move towards the opposite poles of the cell. The separated chromatids are called daughter chromosomes. The daughter chromosomes are pulled to the opposite poles of the cell by the contraction of the fibers of the spindle attached to centromere.
8Telophase: The identical sets of chromosomes at each pole of the cell uncoil and form chromatin threads. The nuclear envelope forms around each chromatin mass, nucleoli reappear and mitotic spindle disappears.
Cytoplasmic Division
Cytoplasmic division begins in late anaphase or early telophase of mitosis. A slight indentation of the plasma membrane called cleavage furrow appears midway between the centrosomes (equatorial plane) and extends around the periphery of the cell. The plasma membrane is pulled progressively inward due to contraction of the actin and myosin filaments in the contractile ring. The contraction ring constricts the centre of the cell and ultimately pinches the cell into two (Fig. 1.3). When cytokinesis is completed, the cell enters the interphase stage of next cell cycle.
Reproductive Cell Division or Meiosis
The division of germ cells is called meiosis. It involves reduction in the number of chromosomes to half the original number. Male and female reproductive cells divide meiotically to form gametes which fuse to form a diploid organism.
Meiosis is divided into two stages (Fig. 55.1):
- Meiosis I
- Meiosis II
Meiosis I
Nuclear division of meiosis I is divided into:
- Prophase I
- Metaphase I
- Anaphase I
- Telophase I
Prophase I
This is the longest phase. The homologous chromosomes, one derived from each parent, pair along their entire length.
Individual chromosome of each pair splits longitudinally into two similar chromatids. Thus, each group which initially consisted of two homologous chromosomes becomes four chromatids (tetrad). Enzymes called endonucleases break chromatids into segments and the segments rejoin. During this rejoining, exchange of genetic material between chromatids occurs. This process is called crossing over. This is followed by separation of the paired chromosomes which is called disjunction. The homologous chromosomes separate. The nuclear envelope and nucleolus disappear. Spindle fibers originate from the poles.
Metaphase I
Spindle formation is completed and chromosomes get arranged at the equator of the spindle.
Anaphase I
The two chromosomes of each bivalent move along the spindle to the opposite poles. The diploid number of chromosomes is reduced to haploid number.9
Telophase I
The chromosomes at each pole form chromatin fiber. Nucleolus and nuclear membrane reappear and two haploid daughter nuclei are formed.
Cytoplasmic division is similar to that occurring in somatic cell division.
Meiosis II
This is similar to somatic cell division, but the two daughter cells are quantitatively and qualitatively different from the parent cell before meiosis I. This is due to reduction division and crossing over.
Significance of meiosis II:
- Four haploid daughter cells are formed from a single diploid cell.
- Each cell forms a gamete. The diploid number is restored when the gametes fuse during fertilization so that continuity of species is maintained. Thus, a constant chromosome number is maintained in successive generations.
- Due to crossing over, genetic variation is possible.
APOPTOSIS
Apoptosis is programmed cell death that is genetically controlled. It is a natural phenomenon. Apoptosis is responsible for the degeneration of many unwanted tissues like web in the fingers during fetal life. It is different from necrosis which is a pathological phenomenon. Inflammatory responses are not seen in apoptosis. No leakage of cell contents occurs and neighboring cells remain healthy. Whereas in necrosis, the healthy cells are destroyed, surrounding tissue is affected and inflammatory responses are present. Necrosis is referred to as cell murder where as apoptosis is cell suicide.
Changes in apoptosis
- Changes in apoptosis may involve single cells or cluster of cells.
- During apoptosis, the cells lose their contact with the extracellular matrix via the cell adhesion molecules.
- The apoptotic cell becomes round or oval and the size decreases.
- Fragmentation of nuclear chromatin occurs due to activation of nuclease.
- Proteolysis of cytoskeletal structures occur.
- Nucleus and cytoplasm eventually break up into small cell remnants called apoptotic bodies.
- The apoptotic bodies are either phagocytosed by macrophages or are shed from the epithelial surface.
Significance of Apoptosis
- In fetal life, apoptosis is responsible for the removal of webs between the fingers, and regression of Wolffian or Mullerian duct system in the course of sexual differentiation.
- In females, apoptosis is responsible for the cyclic breakdown of endometrium leading to menstruation.
- Rapid turnover of enterocytes of intestine is due to apoptosis of mucosal cells as they reach the tip of the villus.
Applied Physiology
Abnormalities in genes that regulate apoptosis are associated with many diseases like autoimmune diseases, cancer and neurodegenerative diseases like Alzheimer's disease. Tumor suppressor genes produce proteins that inhibit cell division. Cancers are produced when tumor suppressor genes are damaged. Tumor suppressor gene called p53 on chromosome 17 is very important in preventing cancer. It also induces apoptosis in cells where DNA is abnormal. So, p53 is called guardian angel of the genome.
INTERCELLULAR CONNECTIONS
Cell junctions are contact points between the cell membrane of adjacent cells of a tissue. A group of proteins called cell adhesion molecules help to hold cells in their place in the tissue. The important cell adhesion molecules are integrins, cadherins and selectins. Cell adhesion molecules attach cells to the basal lamina and to each other. Some cell junctions provide channels for ions and molecules to pass from cell to cell.
There are two types of intercellular connections:
- Connections that fasten the cells to one another and to the surrounding tissues, which include tight junctions, desmosomes, zonula adherens, hemidesmosomes and focal adhesions.
- Connections that permit transfer of ions and molecules from one cell to another, e.g. gap junctions.
Tight Junctions or Zonula Occludens
Tight junctions connect apical margins of adjacent cells to one another strongly. They are made up of ridges, half from one cell and half from the other (Fig. 1.4). The ridges adhere so strongly that there will be no space between the cells at the tight junctions. They are seen in the epithelium of gastric and intestinal mucosa, urinary bladder, renal tubules and choroid plexus.
Functions of tight junctions
- Tight junctions provide strength and stability to the tissues.
- In the brain, tight junctions between the endothelial cells of cerebral blood vessels contribute to the effectiveness of blood-brain-barrier.
Zonula Adherens
Zonula adherens is located below the base of tight junctions and is a cell to cell anchoring junction. It contains the cell adhesion molecules cadherins.
Desmosomes
Desmosomes are the junctions characterized by focal thickening of two adjacent cell membranes. At the thickened part, the intercellular space contains intermediate filaments and cadherins (Fig. 1.4). They attach cells to one another and are mainly seen between cells of epidermis and cardiac muscle cells. Desmosomes prevent cells from pulling apart during contraction especially in cardiac muscle cells.
Hemidesmosomes
Hemidesmosomes appear like half desmosomes and they anchor cells to the basement membrane and not to each other.
Focal Adhesions
Focal adhesions attach cells to the basal lamina. They are associated with actin filaments inside the cell and they play an important role in cell movement.
Gap Junctions
Gap junctions form tunnels that join the cytoplasm of two cells. Normally, the width of the intercellular space is 25 nm. But at gap junctions, the intercellular space narrows to 3 nm. They are made up of special transmembrane proteins known as connexons (Fig. 1.4).
Functions
- Gap junctions permit substances to pass from one cell into the adjacent one without entering the ECF. For example, ions, sugars, amino acids and certain chemical messengers like hormones pass from one cell to another through the gap junctions.
- Since it allows ions to pass from one cell to the next cell it helps in rapid propagation of electrical activity from cell to cell in certain tissues like cardiac muscle.