CELL PHYSIOLOGY

3.1 Introduction – what is a cell?A cell is the structural and functional unit of a living organism. A cell is the smallest unit of

the living thing that has characteristics of life, and it is ooften called the building block of life. Each capable of growth, metabolism, response to stimuli, and, with some exceptions, reproduction. There are two types of cells, namely Eukaryotic cells (these are cells that have a nucleus e.g. muscle cells), and Prokaryotic cells (these are cells that do not have a nucleus e.g. most bacterial cells).

Some organisms are unicellular (these are made up of only one cell e.g. most bacteria), others are multicellular. Humans are multicellular. Similar cells make up tissues, tissues form organs (e.g. pancreas, liver), organs working together form organ systems (e.g. gastrointestinal system), and organ systems make up the organism.

All human tissues are composed of cells. Cells in each tissue have special structural modifications to suit their functions. There are some 200 different types of cells in the body. The human body contains about 100 trillion cells; and, a typical cell size is 10 µm; a typical cell mass is 1 nanogram. The largest known animal cell is an unfertilized ostrich egg cell.3.2 General characteristics of a cell

The general characteristics of a cell include:1] It can take in nutrients and oxygen; 2] It produces its own energy for its needs (metabolism, i.e. and converts nutrients into energy to carry out specialized functions), e.g. growth, function and other activities;3] It eliminates its wastes (carbon dioxide and other metabolic wastes);4] It maintains its medium, i.e. the environment, for its optimal function and survival;5] It responds to the entrance of toxic substances and invasion of bacteria into the body;6] It can reproduce by division. Exceptions such as neurons (performs highly specialized function, RBC (no nucleus) and gametes (mature gamete once they exit meiotic cycle) do not reproduce.3.3 Structure of the cell

Each cell is surrounded by a cell membrane which separates the fluid medium within the cell, the cytoplasm, from the fluid surrounding the cell (ECF). The cytoplasm contains a variety of organelles, which are also bounded by membranes similar in structure to the cell membrane.

Basic components of a cell

The cell can be said to be made up of:1] The cell membrane;

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2] The cytoplasm, which contains a variety of organelles such as mitochondria, lysosomes, centrioles, endoplasmic reticulum, Golgi apparatus, filamentous cytoskeleton, and microtubules;3] The nucleus, a membrane-delineated compartment in the cytoplasm that houses the eukaryotic cell's DNA.

In addition, the cell contains many proteins, e.g. actin and myosin which provide the cell with strength, mobility and mechanism for adhesion to other cells. 3.4 The cell membrane

The cell membrane is a protective sheath enveloping the cytoplasm of the cell. This membrane serves to separate and protect a cell from its surrounding environment. It separates the extracellular fluid (ECF) from the intracellular fluid (ICF). The cell membrane functions as a semipermeable membrane or barrier, thus allowing exchange of certain molecules between the ECF and ICF, while excluding others. The cell membrane is also called plasma membrane.

Structure of the cell membrane

Line diagram of a cell.

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Line diagram of cell membrane

Functions of cell membranesA] supporting and retaining the cytoplasmi. The cell membrane protects the cytoplasm and organelles present in the cytoplasm.ii. The cell membrane is responsible for the shape and size of the cell.

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B] being a selective barrieriii. It acts as a semipermeable membrane which allows some substances to pass through it, but acts as a barrier to other substances.iv. It maintains a constant and unique intracellular environment necessary for the optimal function of the organelles.v. It maintains a constant cell volume by actively pumping out sodium out of the cell.vi. It maintains a potential difference between ICF and ECF in nerves and muscles. This enables these cells to respond to stimuli and transmit information throughout the nervous system and to muscles.vii. The metabolites and other waste products from the cell are excreted through the cell membrane.viii. Exchange of gases and other nutrients occur across the cell membrane, e.g. oxygen diffuses into the cell from the blood and carbon dioxide diffuses out.C] transportix. Certain plasma membrane integral proteins are involved in passage of molecules through the membrane. Some function as carrier proteins through which a substance can simply move across the membrane; others function as carrier proteins that combine with the substance to help it move across the membrane. Others are transported by vacuole formation (vesicular transport). These processes are used to transport biologically useful molecules in and out of the cell.D] communication (via receptors)x. Some integral proteins function as receptors. Each type of receptor protein has a shape that allows a specific molecule to bind to it. The binding of a molecule, such as a hormone (or other signal molecule), can cause the protein to change its shape and bring about a cellular response. Some plasma membrane proteins are enzymatic that carry out metabolic reactions directly.E] recognitionxi. It plays an important role in the ability of certain cells to recognize the individuals own cells and foreign cell or foreign bodies, so they can be destroyed by phagocytosis, antibody formation or cell rejection.F] CompartmentalizationThe cell membrane separates the ECF from the ICF.3.5 Structure of the cell (plasma) membrane

The plasma membrane is a phospholipid bilayer in which protein molecules are either partially or wholly embedded. The phospholipid bilayer has a fluid consistency comparable to that of light oil. Various protein molecules are inserted into or attached to it. The proteins are scattered throughout the membrane forming a mosaic pattern. This is known as the fluid-mosaic model of membrane structure. This was proposed by Singer and Nicolson (1972). The fluidity of the cell membrane, which is dependent on its lipid components, is critical to the proper functioning of the membrane’s proteins. The mosaic pattern of proteins is dependent on the proteins, which vary in structure and function. The plasma membranes of various cells have their own unique collection of proteins. Electron micrographs of freeze-fractured membrane support the fluid-mosaic model.

The cell membrane is composed of proteins (55%), lipids (40 %) [phospholipids (25%), cholesterol (13%), other lipids like glycoprotein (2%) and carbohydrates (5%). Actual proportions vary depending on the type of cell. The constituents of the cell membrane continue to be renewed by the endoplasmic reticulum. Phospholipids in the cell membrane spontaneously arrange themselves into a double layer of lipid molecules called lipid bilayer, which constitute the thickness of the entire cell membrane. It is about 5-8 nm thick.

Membrane Lipids; The major lipids of the cell membrane are phospholipids (e.g. phosphatidylcholine, sphingomyelin, phosphatidylserine, and phosphatidylethanolamine), glycolipids and cholesterol. Glycolipids are generally located in the outer layer. Membrane phospholipid molecules are amphipathic (Gk: amphi means both; they have a polar hydrophilic (water loving) head, and two non-polar hydrophobic (water-hating) tail). The two layers of the phospholipids are arranged such that the hydrophobic tail portions meet in the centre of the membrane. The hydrophilic head portions of the outer layer face the ECF and those of the inner layer the ICF. Glycolipids have a structure like phospholipids. However, the hydrophilic head is a variety of sugar which assist in various functions. Glycolipids only on the outside surface.

The cholesterol molecules are arranged in between the phospholipid molecules (hydrophobic regions). Cholesterol is usually found in animal cell membranes. Cholesterol helps to pack the phospholipids in the membrane and ensures the structural integrity of the cell membrane. Cholesterol reduces the permeability of the membrane to most biological molecules.

The individual phospholipid molecules can move freely within their specific layer (but not from one layer to another). Thus, the cell membrane is fluid in nature, and is not a solid structure and this is termed the fluid mosaic model of the cell membrane. The fluidity of the cell membrane, which is

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dependent on its lipid components, is critical to the proper functioning of the membrane’s proteins. Cellular membranes are fluid mosaics of proteins and lipids. Membrane proteinsThe mosaic pattern of a membrane is dependent on the proteins, which vary in structure and function. The plasma membranes of various cells and membranes of various organelles have their own unique collection of proteins. The proteins form different patterns according to the membrane and within the same membrane at different times. Peripheral proteins are found on the outside and inside of the membrane; while, integral proteins span the lipid bilayer and often have attached carbohydrate chains. Proteins can move laterally in the membrane.

The plasma membrane is asymmetrical: the two halves are not identical. The carbohydrate chains of the glycolipids and proteins occur only on the outside surface and the cytoskeletal filaments attach to proteins only on the inside surface.

The lipid bilayer of the cell membrane forms a semipermeable membrane between the ECF and ICF, which allows only fat-soluble substances to pass through it. For e.g. oxygen carbon dioxide, alcohol. It forms a barrier to water-soluble substances like glucose, urea, and electrolytes.3.6 Membrane proteins

Protein content of the cell depends on its function. There are two main groups; namely, peripheral and integral proteins depending on whether they span the membrane or are present on only one side. 3.6.1 Peripheral proteins

These protein molecules are inserted in the outer or inner leaflet or bound to the cytoplasmic surface. This group of proteins does not penetrate the cell wall. They are loosely bound with the cell membrane and so can dissociate readily from the cell membrane.

Many of the peripheral proteins, e.g. spectrin, bind with the hydrophilic heads of the lipids on the cytoplasmic side or to the integral proteins and connect the membrane intracellularly with the cytoskeleton of actin and other microfilaments which maintain cell shape.3.6.2 Integral proteins

Integral proteins molecules span through the entire thickness of the cell membrane (transmembrane proteins).

Transmembrane proteins serve as: 1] channels or pores through which water-soluble substances can diffuse across the cell membrane (gateway proteins); 2] carriers which transport substances by facilitated diffusion; 3] ion pumps (or transport proteins) which actively transport ions across the membrane; 4] receptors which when activated initiate physiological actions inside the cell.3.6.2 Functional classification of membrane proteins

Channel proteins: Proteins that provide passageways through the membranes for certain hydrophilic or water-soluble substances such as polar and charged molecules to pass into and out of the cell when activated.

Carrier proteins: Transport substances down their electrochemical gradient. No energy is used during transport; hence this type of movement is called facilitated diffusion.

Transport proteins or pumps: Proteins that spend energy (ATP) to transfer materials across the membrane. When energy is used to provide passageway for materials, the process is called active transport.

Recognition proteins: Proteins that distinguish the identity of neighboring cells. These proteins have oligosaccharide or short polysaccharide chains extending out from their cell surface.

Adhesion proteins: Proteins that attach cells to neighboring cells or provide anchors for the internal filaments and tubules that give stability to the cell.

Receptor proteins: Proteins that initiate specific cell responses once hormones or other trigger molecules bind to them.

Electron transfer proteins: Proteins that are involved in moving electrons from one molecule to another during chemical reactions.

3.7 Glycocalyx or Cell membrane carbohydratesThe cell membrane is covered by a carbohydrate rich layer in its external surface known as

glycocalyx or cell coat. The carbohydrate molecules are oligosaccharides and are covalently linked either to membrane proteins (forming glycoproteins) or lipids (forming glycolipids).

Cells, also, secrete some polysaccharides into its immediate adjacent matrix, which are adsorbed into the cell membrane surface. Thus, the outer layer of the lipid bilayer is covered by a layer of glycoproteins and glycolipids.3.7.1 Functions of glycocalyx

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i. To serve as a protective coat, e.g. preventing unwanted protein-protein interaction between cells.ii. The carbohydrate molecules are negatively charged, and thus, do not permit negatively charged molecules to move in and out of the cells.iii. The glycocalyx from neighbouring cells help in the tight fixation of cells with one another.iv. Some of the carbohydrate molecules act as receptors for some hormones, e.g. insulinv. Some glycoproteins help in temporary cell to cell adhesion e.g. between neutrophils and endothelial cells at sites of inflammation.3.8 Cytoplasm

This is the gel-like material within the cell membrane. It is a fluid matrix, the cytosol, which consists of 80% to 90% water, salts, organic molecules and many enzymes that catalyze reactions, along with dissolved substances such as proteins and nutrients. The cell membrane keeps the cytoplasm from leaking out. It contains different organelles which are the insoluble constituents of the cytoplasm.3.8.1 Functions of the cytoplasm

i. The cytoplasm serves as the medium in which organelles are suspended.ii. The cytoplasm surrounds the nuclear membrane and the cytoplasmic organelles. iii. It plays a mechanical role by moving around inside the membrane and pushing against the

cell membrane helping to maintain the shape and consistency of the cell and again, to provide suspension to the organelles.

iv. In addition, it is a storage space for chemical substances indispensable to life, which are involved in vital metabolic reactions, such as anaerobic glycolysis and protein synthesis.

3.8.2 Cytoplasmic organellesThe organelles with limiting membrane vesicles:

i. Endoplasmic reticulumii. Golgi apparatusiii. Lysosomeiv. Peroxisomev. Centrosome and centriolesvi. Secretory vesiclesvii. Mitochondriaviii. Nucleus

The organelles without limiting membranei. Ribosomesii. Cytoskeleton

3.8.3 Functions of cytoplasmic organellesOrganelles FunctionsRough endoplasmic reticulum

i. Synthesis of proteinsii. Degradation of worn out organelles

Smooth endoplasmic reticulum

i. Synthesis of lipids and steroidsii. Storage and metabolism of calciumiii. Degradation of toxic substances

Golgi apparatus Processing, packaging, labelling and delivery of proteins and lipidsLysosomes i. Degradation of macromolecules like bacteria

ii. Degradation of worn out organellesiii. Secretory function

Peroxisomes i. Degradation of toxic substances like hydrogen peroxideii. Oxygen utilizationiii. Breakdown of excess fatty acidsiv. Acceleration of gluconeogenesis from fatsv. Degradation of purine to uric acidvi. Role in the formation of myelin and bile acids

Centrosome Movement of chromosome during cell divisionMitochondria i. Production of energy

ii. Synthesis of Adenosine triphosphate (ATP)iii. Initiation of apoptosis

Ribosomes Synthesis of proteinsCytoskeleton i. Determination of shape of the cell

ii. Stability of cell shape

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Organelles Functionsiii. Cellular movements

Vacuoles Serve to carry materials to the cell membrane for discharge to the outside of the cell.

3.9 NucleusIt controls the cell and houses the genetic material (DNA). The nucleus is the largest of the cells organelles. Cells can have more than one nucleus or lack a nucleus all together. Skeletal muscle cells contain more than one nucleus whereas red blood cells do not contain a nucleus at all. The nucleus is bounded by the nuclear envelope or membrane, a phospholipid bilayer like the plasma membrane. Also, visible within the nucleus are one or more nucleoli, each consisting of DNA in the process of manufacturing the components of ribosomes. Ribosomes are shipped to the cytoplasm where they assemble amino acids into proteins. The nucleus also serves as the site for the separation of the chromosomes during cell division.Functions of the nucleus include:

i. Control of all activities of the cellii. Synthesis of Ribonucleic acid (RNA)iii. Sending genetic instruction to cytoplasm for protein synthesisiv. Formation of subunits of ribosomesv. Control of cell divisionvi. Storage of hereditary information in genes (DNA).

3.10 Cell Cycle and ReproductionCells have the innate ability to reproduce independently. In the gastrointestinal tract, cells reproduce often, while in the nervous system cells reproduce less frequently. The cell cycle is the repetition of cellular growth and reproduction. It is divided into two major periods: interphase and mitosis.

Interphase is the period in which the cell spends most of its time performing its unique functions. Mitosis is the period of the cell cycle during which the nucleus of the cell replicates, followed by the cytoplasm into two daughter cells. The actual division of the cell is known as cytokinesis.

Phase ActivityInterphase G1 Normal cell activities

S Synthesis of DNA, proteins and centriolesG2 Microtubule proteins form spindle apparatus; chromatin begins condensing.

Mitosis Prophase Duplicated chromosomes coil, nucleus and nucleolus disappear, spindle apparatus is completed, and chromosomes move to centre of the cell.

Metaphase Centromeres line up on metaphase plate.Anaphase Centromeres split, chromosomes move to opposite spindle poles.Telophase Chromosomes uncoil, nucleus and nucleoli form, spindle apparatus is

dismantled, and cytokinesis is completed.Cytokinesis Cleavage furrow is formed by contracting microfilaments in animal cells;

the cell’s cytoplasm is divided by cleavage.

The G1 phase follows mitosis and represents the time the cell is synthesizing its structural proteins and enzymes. The chromosomes exist as chromatin. During the S phase of the cell cycle, the DNA replicates within the nucleus. Each chromosome is faithfully copied. At the end of the S phase, there are two chromatids for each one chromosome present in the G1 phase. In the G2 phase the cell prepares for mitosis. Spindles are formed from microtubules in the cell. The nuclear material still exists as chromatin.

In prophase, mitosis begins. Chromatin material in the nucleus condenses to form visible threads. Two copies of each chromosome, called chromatids, exist. The two chromatids are joined together at the centromere. The nucleoli disappear and the nuclear envelope dissolves. Centrioles migrate to opposite poles of the cell, they are attached to radiating spindle fibres extending from opposite ends of the cell. The chromatids attach to the spindle fibres at the kinetochore, a region of DNA that has remained undivided. All pairs of chromatids eventually reach the equatorial plane (centre of the cell), and line up across the centre of the cell bringing prophase to an end.

At metaphase, all pairs of chromatids are lined up at the equatorial plane (metaphase plate). In humans, 92 chromatids in 46 pairs exist at the equatorial plane. Each pair is connected at the

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kinetochore where the spindle fibre is attached. The DNA at the kinetochore duplicates and the two chromatids separate from one another, each forming a chromosome.

At anaphase, the chromosomes move apart from one another, each attached to a spindle fibre. They are drawn to opposite poles of the cell. A total of 46 chromosomes move to each pole of the cell.

In telophase, the chromosomes have moved to opposite poles of the cell. The chromosomes fade from sight, and form masses of chromatin. The spindle is dismantled, its amino acids are recycled; the nucleoli reappear; and the nuclear envelope reforms.

Cytokinesis is the process in which the cytoplasm divides and two separate daughter cells are formed. It begins with the formation of furrows in the equatorial plane and the cell membrane pinches into the cytoplasm. This process is referred to as cleavage. Microfilaments contract during cleavage and assist in the division of the cell.

Mitosis and cytokinesis permit the entire body to grow by forming new cells. It also aids in replacing older cells and those that have been injured.

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