CONTENTS:~ DEFINITION INTRODUCTION CELL MEMBRANE LIPIDS PROTEINS CARBOHYDRATES INTERCELLULAR JUNCTIONS CELL-MEMBRANE~CYTOPLASMIC INTERACTION ENDOPLASMIC RETICULUM RIBOSOMES

MITOCHONDRIA GOLGI COMPLEX LYSOSOMES PEROXISOMES

 CYTOSKELETON MICROFILAMENTS INTERMEDIATE FILAMENTS MICROTUBULES CENTRIOLES PROJECTION FROM THE CELL SURFACE CILIA FLAGELLA MICROVILLI AND BASOLATERAL FOLDS NUCLEUS MITOSIS MEIOSIS CONCLUSION

Cell is the smallest structural and functional unit which forms the building blocks of life.

 INTRODUCTION Robert Hook (1665) in his book named MICROGRAPHIA mentioned about structure resembling honey comb. He called it CELL derived from latin word Cellula meaning small room. German scientists M.Schleinden and T.Schwann (1838-39) proposed CELL THEORY~ i) All organisms were made up of cell. ii) the cell was the basic unit of structure and function of all oranisms.

HONEYCOMB SHAPED CORK CELL

 Cellular Organisation:~ i)Prokaryotes-without delimited nucleus. e.g: bacteria,blue-green algae. ii)Eukaryotes- nucleus delimited with membrane. e.g:Humans, mammals,plants etc. Humans are multicellular with 1014 cells. A typical human cell size is 10microns, typical mass 1nanogram. The largest cell are about 135microns are in the anterior horn in the spinal cord. Smallest are the granular cell in the cerebellum. Longest cell can reach from the toe to the lower brain stem (pseudounipolar cell). The largest known cell are unfertilized ostrich egg.

 The components of the cell can be discussed under 3 headings~ i) Cell membrane ii)Cytoplasm iii)nucleus

 CELL MEMBRANE / PLASMA MEMBRANE / UNIT MEMBRANE~ It is the outer boundary of the cell. Function~ i)Regulates the internal environment of the cell. ii)Determines the immunological makeup of the cell and tissues. iii)Cholestrol molecules add structure rigidity to the cell. iv)The number,makeup,position and mobility of the protein molecules account for specific individual properties of cells and tissues by forming specific receptor molecules.

 Under light microscope mammalian cell structures cannot be seen. Under high magnification electron microscope cell membrane appear as trillaminar structure measuring 75Ao in width (25Ao each). Davson-Danielli concept of semipermiable nuclear membrane has been replaced by FLUID-MOSAIC MEMBRANE theory 1st proposed by Singer.

 Cell membrane is madeup of lipids,proteins snd carbohydrates. LIPIDS~ Trilamminar structure of membrane is produced by the arrangement of lipid molecules(phospholipids). Each phohospholipid molecule have~
i)polar head end,hydrophilic and stains dark. ii)two thin nonpolar tails,hydrophobic and stains light.

 Types of phospholipids are phosphotidylcholine,phosphotidylserine ,phosphotidylethanolamine and sphingomyelin. Cholestrol provides stability to the membrane. Glycolipid are present on the outer surface of the membrane. Galactocerebroside which is an important constituent in myelin sheath.

 PROTEIN Forms 50%massof the membrane. Functions~ i) Forms cell adhesion molecules. ii)As pumps actively transporting ions across the membrane. iii)As carrier transporting substance by facilitated diffusion. iv)As receptors for neurotransmitters and harmones. v)As enzymes

 The protein which are embedded and pass through the membrane are called Integral Protein. Proteins attatched to the surface of the membrane are called peripheral proteins. Hydrophobic portion of protein located in the interior of the membrane. Hydrophilic portion located on the surface. Commonly proteins are attatched by glysylphosphatidylinisitol anchors.

 Other proteins are lipidated that is they have lipid attatched to them. CARBOHYDRATES The carbohydrates layer on the external surface of plasma membrane forming cell boundry reffered to as the Cell Coat or Glycocalyx. Carbohydrates attatched to~ proteins form glycoprotein. Lipids form glycolipid. This layer contains antigen ,include Major Histocompatibility antigen, In erythrocytes the glycocalyx contain Blood Group Antigen.

 Special adhesion molecules present enables the cell to adhere to specific type of cells and extracellular molecules. Glycocalyx has got ve charge which causes repulsion with cells of same charge mainting a distance of 20nm, Whereas cells wih opposite charge are held together. Some glycoprptein molecules present in the cell membrane are called Cell Adhesion Molecules(CAM).

 The intermediate protein holds the CAM in the cytosolic end of the cell. Some CAM are calcium dependent while some are calcium independent~

Type of CAM

Subtypes Cadherin(of various types)

Present In Most cells including epithelia. Migrating cells.e.g. leucocytes. B/w cells and intercellular substance(20 types).

CALCIUM DEPENDENT Selectins

Integrins

CALCIUM INDEPENDE NT

Neural cell adhesion molecule(NCAM) Intercellular adhesion molecule(ICAM)

Nerve cells. Lecocytes.

 Intermediate protein are~catenins,vinculin,alpha actinin. INTERCELLULAR JUNCTION~ Ciassified as1)Occluding(tight junction) or Zona occludens. 2)Adhesive junctions a)cell-to-cell i)zonula adherence(Adhesive belts) ii)Macula adherens(Desmosomes or adhesive spots)

b)Cell-to-matrix i)focal adhesion ii)Hemidesmosomes. 3)Communicating gap junction. 1)Occluding(tight) junctions or Zona occludens~ Cell membranes held by transmembrane adhesive proteins arranged anastomosing strands that encircles the cell. Intercellular space obliterated completely. Gaps may b present allowing slow diffusion of molecules reffered to as leaky tight junction.

 2)i)Zonula Adherence(adhesive belts) Plasma membrane thickened because of the presence of a dense layer of protein on its surface. The thickened area of the two sides are separated by a gap of 25nm and is rich in glycoprotein This forms a continous bsnd around the epithelial cell. The CAM present are Cadherins.

 ii)MaculaAdherens (desmosomes,adhesive spots) Most common type of junction b/w adjoining cells. Desmosomes are present where strong anchorage b/w cells are needed.e.g.b/w cells of epidermis. These are small circumscribed area of attatchment. The gap b/w the thickenings of the membranes are held together by fibrils. CAM seen in desmosomes are cadherin. The link proteins are desmoplakins.

DESMOSOME.

 B)i)FOCAL ADHESIONS PLAQUES/FOCAL CONTACT. In focal adhesions the transmembrane components is a member of the integrin family of adhesion molecules. Such contacts may send signals to the cell and initiate cytoskeleton formation . HEMIDESMOSOMES Similar to desmosomes ,but the thickening of the membrane is seen only on one side. The external ends of CAMs are attatched to the extracellular structure. Cytoskeleton attatched to intermediate protein are keratin, CAMs are integrins. GAP JUNCTION Plasma membrane are not in actual contact, the being reduced from 20nm to 3nm.

 In transmission electron microscope this gap is seen containing bead like structure. A minute canaliculus passing through each bead connects the cytoplasm of the two cells thus allowing the free passage . the gap junctions are therefore also called Maculae Communicants. Changes in ph or in calcium ion concentration can close the channels of gap junctions. Channel are arranged in hexagonal groups. Wall of each channel is made up of 6 protein element called Nexins or Connexons. Inner end projects into the gap between the two cell membrane. Here similar nexins come in contact with similar nexins projecting into the space from the cell membrene of the opposite cell, to complete the channel. Electric synapsis between some neurons.

 CELL MEMBRANE CYTOPLASMIC INTERACTION. Cell function depends on signals and nutrients received through the cell membrane. Molecular movement within the cellCapping. Larger molecules enter the cell by the process of Endocytosis. Absorption of fluid into the cell by vesicles are called as Pinocytosis. Process of endocytosis to engulf foreign matter (bacterias) is refferred to as Phagocytosis.

 Releasing the molecules to the exterior are called Exocytic Vesicle and the process is called as Rverse Pinocytosis. Area marked by the presence of Fusogenic proteins aid the formation of endocytic and exocytic vesicles. Receptor mediated endocytosis are seen in depressed area called Coated Pits. The membrane the floor of the pits is thickened due to the presence of a protein called Clathrin.

 Process of transferring materials right through the thickness of a cell is called Transcytosis. The transport takes place through invagination of cell membrane called Caveole. Protein caveole is associated with caveole.

 CYTOPLASM Cytoplasm of a typical cell contains various structures that reffered to as Organelles. They are~ ENDOPLASMIC RETICULUM:~ The membrane form the boundries of channels that may be arranged in the form of flattened sacs (or cisternae)or tubules. Cytoplasm within the channel is called as Vaculoplasm and that outside the channel is the Hyaloplasm or Cytosol. Membrane forming the endoplasmic reticulum are studded with minute particles of RNA called Ribosomes giving rough appearance ,so they are called Rough/Granular Endoplasmic Reticulum.

 Membrane devoid of these ribosomes are called as Smooth/ Agrannular Endoplasmic Reticulum. Rough endoplasmic reticulum represents the site of protein synthesis. Ribosomes play a very important role this process. They are in continuation with nuclear membrane. Smooth endoplasmic reticulum are involved with the ~ i)production of lipids. ii)carbohydrates metabolism. iii)Detoxification of drugs and poison. iv)Metabolizing calcium to mediate some cell activities. v)Releases calcium to trigger muscle contraction.

 RIBOSOMES- PROTEIN PRODUCTION MACHINE All living organism contain ribosomes composed of appox.60%(rRNA) and 40%protein. Eukaryotes ribosome are made of 4 strands of RNA. Prokaryotes ribosomes consists of 3 strands of RNA. They may lie free in cytoplasm or in relation to rough endoplasmic reticulum.

 Present singly-Monosomes. In groups-polyribosomes. It is made up of 2 subunits, 60s and 40s.

Thy engage in protein synthesis~ Free ribosomes for cell`s own use. Attatched ribosomes-for extracellular use.

 MITOCHONDRIA~THE POWER GENERATORS OF THE CELL. The term mitos=granule; chondrium=rod. They vary in size and no, most being 0.5microns to 2microns in length. These cells are high in high metabolic activity.(e.g secretory cells). It is bounded by outer and inner membrane. The two are separated by an Intermembranous Space.

 The inner membrane is highly folded on itself forming incomplete partition called Cristae. Space bounded by inner membrene is filled by granular material called Matrix. It contains some RNA and DNA which carry information enables mitochondria to duplicate themselves during cell division. All mitochodrias are maternal in origin since they are from unfertilized ovum. Mitochondrial DNA can be abnormal resulting in disorder reffered as Mitochondrial Cytopathy Syndrome.

 In this muscle weakness, degenerative lesions in the brain and high levels of lactic acid. Mitochondria contein many enzymes some of which play an importsnt part Kerbs cycle(TCA cycle). Enzymes for conversion of ADP to ATP are located in the intermembranous space. Enzymes for lipid synthesis and fatty acids metabolism are located in the outer membrane.

ENDOSYMBIOTIC THEORY symbiosis-living together Lynn Margulis 1971. Mitochondria and chloroplast derived from ancient colonization of large (become eukaryotic cell) by smaller bacteria. Host cell acquires respiration from the precursor of mitochondrion and chloroplast. Also acquires genetic information. Eventually organelle lost the ability to exist as independent organisms.

MITOCHONDRIA.

 GOLGI COMPLEX These organelle consists of a series of parallel doughnut shaped flat spaces or cisternae. They are of irregular shape usually near the nucleus. Towards the margin of the flattened sacs ,small rounded vesicles are present. Functional point if view golgi complex is divisible into 3 regions~ i)A region nearest the nucleus is the cis face(cis golgi). ii)opposite face(near the cell membrane)is the trans face. iii)The intermediate part as the medial golgi.

 Cis faceProtein are phosphorylated. Medial golgiHere sugar residues are added to proteins to form protein-carbohydrate complexes. Trans facei)Proteolysis of some proteins convert them from inactive to active forms. ii)adding sugar residues to protein. iii) substance are sorted out and packet in appropriate vesicles.

GOLGI COMPLEX

 As protein pass through successive sacs of golgi they undergo a process of purification. LYSOSOMES:- (LYTIC BODIES) These are bags of hydrolysing enzymes that break down a large variety of substance which could serve as nutrients or raw material for biosynthetic activity. Sometimes it digests the whole of the cell or a part of it thats its referred as Suicide Bags. Lysosomes belong to the acid vesicles system.

LYSOSOMES

 Its membrane acts as the Hydrogen pump.The stages in the formation of a lysosomes are as follows~ i)Acid hydrolase enzyme which are formed in endoplasmic reticulum are inactive due to lack of acid medium- Primary lysosomes. These vesicles fuse with other vesicles (endosomes)producing an acid medium forming- Endolysosome or Secondery lysosomes. With this hydrogen ions are pumped into the vesicles which creates acid environment and activates the enzymes.-Mature lysosomes.

 Lysosomes are present in all cells except mature erythrocyte. Genetic defects can lead to absence of specific acid hydrolse that are normally present in lysosomes.e.g:-lysosomal storage diseases. PEROXISOMES-CELLULAR DIGESTIVE SYSTEM. These are membrane bound vesicles containig enymes. Contains enzyme catalase which destroys hydrogen peroxide thus preventing the hydrogen accumulating in the cell. Most prominent in the liver and in renal tubules.

 CYTOSKELETON~ The Cell Scaffold. It provides i)Structural framework. ii)facilitates intracellular transport, iii)Supports cell junctions, iv)transmits signals about cell contact and adhesion. v)Permits motility. 3 Structural elements of the cytoskeleton are~ i)Microfilaments. ii)Intermediate filaments iii)Microtubules.

 MICROFILAMENTS~ They are made up of protein actin,these are molecules of (G-actin) which polymerises to form long chains called F-actin,actin filaments and microfilaments. Actin filaments form a meshwork just subjacent to the cell membrane called Cell Cortex. This maintains the shape of the cell. The filement forming meshwork are held together by a protein called Filamin. The filaments can separate and reform in different orientation that is how shape of a cell is altered.

 INTERMEDIATE FILAMENTS~ They are so called as their diameter is intermediate between that of microfilaments (5nm) and of microtubules(25nm). They includecytokeratin- In epithelial cell. Neurofilament protein-Neurons. Desmin-Muscles. Glial fibrillary acidic protein-In astrocytes. Laminin-In the nuclear lamina of cells. Vimentin-In many types of cell.

 These filaments facilitates cell attachment to extracellular elements at hemidesmosomes. In the epithelium of the skin the filaments undergo modification to form Keratin, they also form the main constituents of hair and nails. The neurofilaments of neurons are intermediate filaments and these helps in maintaining the cylindrical shape of the axons. The nuclear lamina contains the intermediate filaments.

 MICROTUNULES:-25microns in diameter. Basic constituents of microtubules is the protein tubulin. The chain of tubulin form Protofilaments which run longitudinally. The tubulin protofilaments are stabilised by microtubule associated protein(MAPs). Microtubule are formed in centrioles which constitute a microtubule organising center.

 The role of microtubule are:~ i) They provide stability to the cell. They prevent tubules of endoplasmic reticulum from collapsing. ii)Facilitates transport within the cell. iii)In dividing cells microtubules from the mitotic spindle. Cilia are made up of microtubules (held together by proteins). CENTRIOLES~ These are paired organelles found together near the nucleus located at right angles to each other . Each centriole is made up of nine bundles of microtubules arranged (3 per bundle) in a ring. They have role in building cilia and flagella during which they are referred to as Basal Bodies.

 These are seen as mitotic spindles in mitosis and meiosis. These structures are self replicating . VACUOLES~ Membrane bound sacs for storage digestion and water removal. PROJECTION FROM THE CELL SURFACE Many cells show projections from the cell surface. The various types of projections are~ 1)CILIA~ These are minute hair like projections from the surface of the epithelium. The free part of the cilium is called the Shaft. The region of attachment of the shaft to the cell surface is called the Base. The extension of cell membrane forms the outer covering .

 The microtubules arranged in a definite manner forms the inner core. There is a central pair of tubules ,the outer tubules are connected to the inner pair by radial structure (which are like spokes of a wheel). FUNCTIONS~ Cilia lining the epithelial surface move in coordination with one another the total effect being that like a wave. It lines the respiratory tract helps in movement of secretion. Helps in movement of ova through the uterine tube. Spermatozoa through male genital tract.

 Cilia like structure that perform some sensory function. E.g: olfactory cilia in nasal mucosa-receptor for smell. Kinocilia in some parts of internal ear. FLAGELLA~ Larger processes having same basic structure of cilia. e.g:flagellum tail of spermatozoon. MICROVILLI AND BASOLATERAL FOLDS~ Microvilli are finger like projections from the cell surface.

CILIA AND FLAGELLA

 Each microvillus consists of an outer covering of plasma membrane and a cytoplasmic core in which numerous microfilaments are continous with actin filaments of cell cortex . e.g straited border epithelial cell lining the small intestine.

 NUCLEUS~(4-10microns in dia) The nucleus is a highly specialized organelle that serves as the information and administrative center of the cell. Two major functions:~ i)It stores the cells hereditary material or DNA. ii)It coordinates the cells activities, which include intermediary metabolism ,growth,protein synthesis and reproduction(cell division). Nuclei appears to be made up of a delicate network of fibres the making up of fibres of the network is called Chromatin

 Some places the chromatin is seen in the form of irregular dark mass called Heterochromatin. At other places the network is loose and stains lightly, such areas of chromatin is refferred to as Euchromatin. Nuclei which are large and in which relatively large areas of euchromatin can be refferred as Open-faced nuclei. Nuclei which are made up mainly of heterochromatin are refferred to as Closedfaced nuclei. The masses of heterochromatin ,the nucleus shows one or more rounded, dark staining bodies called Nucleoli.

CHROMOSOMES~ Chromatin becomes tightly coiled and takes appearance of no of short, thick, rod like structures. Made up of Deoxyribonucleic acid(DNA) Double helix structure- two strands coil. Each DNA strand consists of nucleiotides. Each neucleiotide sugar,phosphate molecule and base. Base-adenine,guanine,cytosine and thymine. Sugar is made of 5C atom9 (pentose). Two chain of neucleotide arranged antiparallel(3-5).

Two parallel rods-like called Chromatids. Joined by centromere (kinetochore). Highly coiled part constrictionPrimary constriction.

It has long arm and short arm. Metacentric-two arms of equal length. Submetacentric-slightly away from center. Acrocentric-Diff is marked. Telocentric-centromere at one end. End of chromatid secondary constrictionnucleolar organizing centers. Distal part satellite.

RIBONUCLEIC ACID(RNA) Contains ribos sugar. Base replaced by uracil. Types of RNA are~ mRNA, tRNA , rRNA. m RNA carries message for protein synthesis to the ribosomes called Transcription. Formation of amino acids by these m RNA and t RNA is celled Translation.

NUCLEOLI 1-3microns in diameter , round in shape, metabolically active. Central filamentous zone-Pars filamentous. Outer granular layer-Pars granulosa. Base Pars amorphousa. Chromosome located near the neucleoli-Pars chromosoma. RNA is synthesized. r RNA (long filamentous,fibrous zone) smaller pieces(ribosomal sub units, granular zone)leaves nucleolus through pores cytoplasm, protein synthesis.

 The space between the various constituents of the nucleus are filled by a base called the Nucleoplasm. The nucleus is seen to be surrounded by double layer membrane or Nuclear envelop. The space between the outer and inner layer is the Perinuclear space. Deep to the inner membrane there is a layer containing protein and a network of filaments ,this layer is called The nuclear lamina. Protein lamins form a scaffolding that maintaining the spherical shape of the nucleus.

 Several points the inner and outer layer of the nuclear membrane fuse leaving gaps called Nuclear Pores. Pore is surrounded by dense protein arranged in the form of 8 complexes. Chromatin is made up of substance called Deoxyribonucleic acid. Protein in the chromatin are Histons. The structure formed by a histone complex and the DNA fibre coiled around it is called Nucleosome.

 Filaments of chromatin are again coiled on themselves called Supercoiling and it is repeated several times. 5 types of histones are recognised H1,H2A, H2B, H3 and H4. Two molecules each of H2A, H2B, H3 and H4 join to form a granular mass, the nucleosome core. DNA filament is wound twice around this core, the whole complex forming a nucleosome. One nucleosome is connected to the next by a short length of linker DNA. During cell division the entire chromatin within the nucleus becomes very highly coiled and takes on the appearance of short, thick and rod like structure called chromosomes.

 The number of chromosomes in each cell is fixed for a given species and in man it is 46. 44 are autosomes and 2 are sex chrosomes. The females sex is described as homogametic and male is heterogametic. Virchow states ~~Every cell is derieved from a cell. Multiplication of cell takes place by division of pre existing cells.

 The daughter cell having chromosomes identical in number and in genetic content to those in the mother cell type of cell division is called Mitosis. The daughter cells having the reduced number of chromosomes to half the normal number and genetic information in the various gametes produced is not identical ,this type of cell division is called Meiosis.

MITOSIS The period during which the cell is actively dividing is the Phase of Mitosis. Equal division of nuclear DNA known as Karyokinesis followed by Cytokinesis. The period between two successive divisions is called Interphase. G1 Stage~The greater part of interphase is this phase. It is the period during which cell carries the normal function. S Stage(synthesis)~12 hrs before the onset of mitosis the synthesis of DNA takes place and is completed in about 7hrs.

 G2 Stage~The last 5hrs before mitosis are utilized for synthesis of protein required for cell division. Cell at G2 stage have a double complement of DNA. Mitosis is divided into number of stages called~ 1)Prophase 2)Metaphase 3)Anaphase 4)Telophase. The later part of metaphase is called Prometaphase.

 Telophase the chromatin of the chromosomes uncoils and elongates and the chromosomes can no longer be identified. During S phase of interphase the DNA content of the chromosomes is duplicated. PROPHASE~ The chromatin of the chromosome become gradually more coiled so that the chromosome acquire rod like appearance. The two centrioles separate and more to opposite poles of the cell and produce a number of microtubules that pass from centriole to the other and form a spindle. The tubules radiating from each centriole create star like appearance or Aster.

 Two aster collectively called as Diaster or Amphiaster or Achromatic spindle. Nuclear membrane breakdown and disappear. METAPHASE~ With the formation of spindle the chromosomes move to a position midway between the two centrioles(i.e, at the equator of the cell) where each chromosomes become attached to microtubules of the spindle by its centromere. The plane along which the chromosome lie during metaphase is the Equatorial Plate or Metaphase Plate.

 ANAPHASE Centromere of each chromosome splits longitudinally into two so that chromatids becomes independent chromosomes. One chromosome of each such pair now move along the spindle to either pole of the cell. This is followed by telophase in which chromosomes gradually elongates and nucleoli reappears. The division of the nucleus is accompanied by the division of the cytoplasm, the cleavage into two separate cells is referred to as Cytokinesis.

 Mitosis can be arrested by chemicals colchicin, it stops mitosis at metaphase and allow us to study chromosomes at this stage. Neurons, cardic muscles do not undergo mitosis and are said to be in G0 phase.

MITOSIS

MEIOSIS Meiosis consists of two successive divisions in which during the 1st division duplication of the DNA content of the chromosomes. 2nd division takes place as in mitosis. 1ST MEIOTIC DIVISION The prophase of the 1st meiotic division is prolonged and usually divided into a number of stages as follows~ a) Leptotene~The chromosomes gradually becomes thicker and shorter. Zygotene~The pairing of the chromosomes occurs which are referred to as Synapsis or Conjugation. The two chromosomes together constitute a bivalent.

 c)Pachytene~ The two chromatids of each chromosomes become distinct. The bivalent now has four chromatids in it and it is called a Tetrad. The two central chromatid becomes coiled over each other so that they cross at a number of points called Crossing Over. The site where the chromatids cross they become adherent. The point of adhesion are called Chiasmata. d)Diplotene~ Crossing over of genetic material each of four chromatids of the tetrad now has a distinctive genetic content.The two chromosome of the bivalent now move apart.

 Metaphase is same as in mitosis. In anaphase there is no splitting of the centromeres. Telophase is similar to that in mitosis. The first meiotic division is followed by a short interphase in which there is no duplication of DNA. SECOND MEIOTIC DIVISION It is similar to mitosis . The DNA content of the daughter cells is reduced to half of the crossing over during 1st division The daughter is not identical in genetic content. In meiosis random shuffling of the genetic material takes place thus no two persons are alike.

 CONCLUSION Thus understanding the ultrastructure of the cell organelles and its functions is very essential for the diagnosis and the treatment plan of various diseases.