A TOUR OF THE CELL 1 Dr.Bhavna Tyagi(PG 1 ST year) 1
content History Defination of cell Types and difference between prokaryotic and eukaryotic Cell theory Basic aspect Cell membrane Cytoplasm and its organelles Function of organelles Cytoskeleton Functional system of cell 2 2
Cell cycle Mitosis and Meiosis Checkpoints in cell cycle Apoptosis 3 3
history Robert Hooke used simple lenses to observe cork in which he saw tiny compartments he called cells ( cellulae) 4 4
What is a cell? 5 5
An aggregate of cells in an organism that have similar structure and function : T issue an organ (or viscus ) is a collection of tissues joined in a structural unit to serve a common function An organism may be either unicellular (a single cell) or comprise many trillions of cells grouped into specialized tissues and organs . cell 6 6
Types of cell 1.Prokaryotic cells :nucleus without membrane eg . Bacteria and Blue green algae 2.Eukaryotic cell : organised nucleus and cell organelles eg . Plants and animals 7 7
Difference between prokaryotic and eukaryotic 8 8
CELL THEORY The Cell Theory 1. Schleiden (a botanist) and Schwann (a zoologist): believed that all plants and animals consist of cells. 2. Virchow: cells come from preexisting cells. The Cell Theory: three generalizations : 1. All organisms are composed of one or more cells. 2. The cell is the smallest unit having the properties of life. 3. The continuity of life arises directly from the growth and division of single cells. 9 9
Basic aspects Structural Organization of Cell All cells have three basic parts : 1. P lasma membrane:- separates each cell from the environment, permits the flow of molecules across the membrane 10 10
2. A DNA-containing region occupies a portion of the interior 3. The cytoplasm contains membrane-bound compartments (except bacteria), particles , and filament all bathed in a semifluid substance Continues… 11 11
Cell membrane B iological membrane that separates the interior of all cells from the outside environment Selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells . P rotect the cell from its surroundings. 12 12
Thin, pliable, elastic structure only 7.5 to 10 nm thick Composed entirely of proteins and lipids Appears to be trilaminar in electron microscope. 13 13
Components of membrane Lipid bilayer Cholesterol Carbohydrates Proteins 14 14
Fluid mosaic model of membrane 15 15
CELL MEMBRANE consist of bilayer of phospholipid molecules that are amphipathic,i.e consist of polar head and nonpolar tail Polar head (water loving) Non polar tail (water hating) 16 16
PHOSPHO LIPID MOLECULE 17 17
CHOLESTROL MOLECULES CHOLESTROL MOLECULES are present in the bilayer(1:1 ratio with the phosphate) Stabilize and regulate the fluidity of the bilayer 18 18
PROTEIN MOLECULES 2 types: (a) Integral proteins: Protrude all way through the membrane. Provide structural channels(or pores ) through which water molecules and water soluble substances(ions) can diffuse between extracellular and intracellular fluid. (b) Peripheral protiens: attached to only one surface . No penetration. 19 19
FUNCTIONS OF TRANSMEMBRANE PROTEIN CELL TO CELL adhesion CELL MATRIX adhesion Formation of pores or channels for the transport of materials into and out of the cell 20 20
GLYCOCALYX Membrane Carbohydrates Occur in combination with proteins and lipids in form of glycoproteins or glycolipids. Entire outside surface of the cell often has a loose carbohydrate coat called “ glycocalyx” 21 21
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Cytoplasm and its organelles 23 23
CYTOPLASM Material enclosed by plasma membrane. Clear fluid portion of the cytoplasm in which particles are dispersed is called “cytosol” Occupies space between plasma membrane and nuclear membrane 24 24
Chemical composition of protoplasm Water:75 -85% Protein :10-12% Lipid:2-3% Carbohydrates:1% Inorganic substances:1% DNA:0.4% RNA:0.7% 25 25
Types of Organelles Nonmembranous organelles : no membrane direct contact with cytosol Membranous organelles : covered with plasma membrane isolated from cytosol 26 26
Non membranous organelles Ribosomes (free ribosomes and polysomes ) Microtubules Centrioles Cilia and flagella Filaments 28 28
THE NUCLEUS Discovered by Robert Hooke in 1831 Is the cell’s control center Contains DNA: genetic material 29 29
The Nucleus contains DNA,protein called as NUCLEOPROTEIN and some RIBONUCLEIC ACID. 2 TYPES OF NUCLEOPROTEIN HISTONE NON HISTONE Control the coiling and expression of the genes encoded by DNA strands n NON PROTEIN HISTONES 30 30
NUCLEI are hetrogenous structures with electron-dense(dark) and electron-lucent(light) HETROCHROMATIN H, consist tightly coiled inactive chromatin found irregular clumps EUCHROMATIN E, represents that part of the DNA that is active in RNA synthesis 31 31
CHROMATIN –collectively , HETROCHROMATIN and EUCHROMATIN are known as CHROMATIN CHROMATIN is a highly organised but dynamic structure with the individual chromosome tending to clump in particular areas of the nucleus ,known as chromosome territories 32 32
THE NUCLEOLUS It is an accumulation of large amount of RNA and proteins. Nucleolus becomes considerably enlarged when the cell is actively synthesizing proteins. 33 33
MICROGRAPH OF NUCLEOLUS F- filamentous component G-granular component The filamentous component are the site for the ribosomal RNA synthesis RIBOSOME assembly take place in the granular component 34 34
NUCLEAR ENVELOPE The Nuclear envelop NE,which encloses the nucleus N,Consist of 2 layers 0f membrane with the INTERMEMBRANOUS or PERINUCLEAR SPACE between 35 35
NUCLEAR PORES The nuclear envelop contain numerous NUCLEAR PORES (NP) at the margins of which the inner and outer membranes become continuous NUCLEAR PORES permit and regulate the exchange of metabolities ,macromolecules and ribosomal subunits between the nucleus and cytoplasm 36 36
Endoplasmic Reticulum This is a complex network or reticulum of membranes running throughout the cytoplasm Walls are constructed of lipid bilayer membranes that contain large amounts of proteins Contain of flattened membrane bound sacs called CISTERNAE 37 37
Endoplasmic Reticulum CONT. Cisternae are storage chambers within membranes 2 types: Rough endoplasmic reticulum Smooth endoplasmic reticulum 38 38
ROUGH ENDOPLASMIC RETICULUM It has ribosomes attached throughout the surface This type of ER is present in the cell which shows active protein synthesis 39 39
Micrograph shows rER tends to b profuse and to form closely packed laminae of flattened cisternae NOTE the close association between the rER and the outer lipid bilayer of the nuclear envelop NE with which its in continuity 40 40
Smooth Endoplasmic Reticulum No ribosomes attached Tubular Membrane 41 41
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GOLGI APPARATUS Golgi apparatus is made up of one or more golgi bodies which are stacks of 3 – 10 flattened sacs and vesicles Closely related to endoplasmic reticulum Prominent in secretory cells. 45 45
GOLGI APPARATUS Vesicles from the endoplasmic reticulum (via the vesicular-tubular clusters ) fuse with the network and subsequently progress through the stack to the trans Golgi network, where they are packaged and sent to their destination. Each region contains different enzymes which selectively modify the contents depending on where they reside. 46 46
FUNCTIONS Formation of cell wall Synthesis of glycolipid Lysosomes formation Water balance Lipid secretion Protein secretion 47 47
Lysosome membrane-bound cell organelle They are structurally and chemically spherical vesicles containing hydrolitic enzymes 250 to 750 nm in diameter. Surrounded by a typical lipid bilayer membrane. 48 48
Enzymes of the lysosomes are synthesised in the rough endoplasmic reticulum . The enzymes are released from Golgi apparatus in small vesicles which ultimately fuse with acidic vesicles called endosomes , thus becoming full lysosomes They are popularly referred to as "suicide bags" or "suicide sacs" of the cell 49 49
Types of lysosomes Primary –these are small vesical like structure produced from the golgi apparatus Secondary-they are formed when phagosomes fuse with already existing primary lysosomes Residual bodies Autophagic vacuoles –these lysosomes envelope and attack intracellular organelles like mitrochondria etc and digest them 50 50
FUNCTIONS Provide an intracellular digestive system that allows the cell to digest within itself (a) damaged cellular structures (b) food particles that have been ingested . (c) unwanted matter such as bacteria. Autolysis of a cell by release of the enzymes with in the cell 51 51
Peroxisomes Are enzyme-containing vesicles Break down fatty acids Membrane sacs containing oxidases and catalases to neutralize free radicals that are formed during catabolism of organic molecules Produce hydrogen peroxide (H 2 O 2 ) Peroxisomes not made by Golgi apparatus rather formed by self-replication. 52 52
Peroxisomes 53 53
MITOCHONDRIA Power house of the cell. Present in all areas of the cell’s cytoplasm. Variable in size n shape 54 54
Two lipid bilayer protein membrane: outer and inner membrane. Many infoldings of inner layer forms shelves onto which oxidative enzymes are attached. Inner cavity of mitochondria is filled with matrix that contains large quantity of dissolved enzymes that are necessary for extracting energy from nutrients. 55 55
The cytoskeleton Cytoskeleton: Supporting framework Three main types : microfilament, microtubules and intermediate filament 56 56
FILAMENTS AND TUBULAR STRUCTURES Microfilaments Thin filaments (<6nm diameter) Composed of the protein actin Usually at periphery of the cell Functions: provide additional strength by attaching the membrane to the cytoplasm Attach integral proteins to cytoskeleton Pairs with thick filaments of myosin for muscle movement 57 57
Intermediate Filaments & Thick Filaments Intermediate Filaments: 7-11 nm diameter Mid-sized between microfilaments and thick filaments Durable , type varies with cell Functions : strengthen cell and maintain shape stabilize position of organelles 58 58
Thick Filaments 15 nm diameter Composed of myosin Muscle cells only Function Interact with actin to produce movement 59 59
Microtubules Large (25nm diameter), hollow tubes Composed of tubulin protein Originate from centrosome 60 60
Functions Foundation of the cytoskeleton Allows the cell to change shape and assists in mobility Involved in transport Makes up the spindle apparatus for nuclear division (mitosis) The structural part of some organelles Centrioles, cilia, flagella 61 61
Centrioles in the Centrosome Centrioles : form spindle apparatus during cell division Centrosome : cytoplasm surrounding centriole near the nucleus Consists of matrix and paired centrioles Responsible for assembling spindle apparatus during mitosis 62 62
Cilia and Flagella Hair like projections Contain a microtubule core with cytoplasm covered in plasma membrane 67 63 63
Cilia: Short, numerous Function: sweep substances over cell surface Flagella: Long, singular Function: propel cell through environment 64 64
FUNCTIONAL SYSTEMS OF THE CELL Ingestion by the cell – ENDOCYTOSIS The plasma membrane envelops small particles or fluid, then seals on itself to form a vesicle or vacuole which enters the cell: Phagocytosis Pinocytosis Receptor-Mediated Endocytosis 65 65
Phagocytosis ( cell eating ) In phagocytosis, a cell engulfs a particle by Wrapping pseudopodia around it and packaging it within a membrane enclosed sac large enough to be classified as a vacuole called as phagosomes The particle is digested after the vacuole fuses with a lysosome containing hydrolytic enzymes. 66 66
phagocytosis 67 67
Pinocytosis ( cell drinking ) Endosomes “drink” extracellular fluid and enclose it in membranous vesicles at the cell surface 68 68
Mitosis and Meiosis Cell cycle Checkpoints in cell cycle Apoptosis These topic will be cover in next seminar 69 69
Bibliography : wheater’s functional histology . A text and colour Atalas . fifth edition Arthur C. Guyton; John E. Hall. Text book of Medical Physiology. Tenth edition. 70 70
THANK YOU 71 71
Cell cycle and replication 72
cell cycle Proliferating cell progress through a series of checkpoints and defined phases called THE CELL CYCLE CELL CYCLE consists of G1,S,G2,M,G0 phases 73
CELL CYCLE cell growth, organelle duplication, protein synthesis, synthesizes enough cytoplasm for 2 cells DNA replication and histone synthesis.8-12 hours after mitosis and 7-8 hrs for completion. finishes protein synthesis and centriole replication Mitosis involves division of the chromosomes. Cytokinesis involves division of the cytoplasm. 74
Cell division Multiplication of cells takes place by division of pre-existing cells. Body (somatic) cells divide in 3 stages: DNA replication duplicates genetic material exactly Mitosis divides genetic material equally Cytokinesis divides cytoplasm and organelles into 2 daughter cells 75
Mitosis What is the purpose of mitosis? Cell division Products genetically identical Growth of organism 76
Stages The period during which the cell is actively dividing is the phase of mitosis The period between two successive divisions is called the interphase Interphase is often included in discussions of mitosis, but interphase is technically not part of mitosis, but rather encompasses stages G1, S, and G2 of the cell cycle. 77
Divided into Prophase Metaphase Anaphase Telophase 78
Interphase The cell is engaged in metabolic activity and performing its prepare for mitosis (the next four phases that lead up to and include nuclear division). Chromosomes are not clearly discerned in the nucleus, although a dark spot called the nucleolus may be visible. The cell may contain a pair of centrioles (or microtubule organizing centers in plants) both of which are organizational sites for microtubules. 79
prophase Chromatin in the nucleus begins to condense and becomes visible in the light microscope as chromosomes. The nucleolus disappears. Centrioles begin moving to opposite ends of the cell and fibers extend from the centromeres. Some fibers cross the cell to form the mitotic spindle. 80
Prometaphase The nuclear membrane dissolves, marking the beginning of prometaphase . Proteins attach to the centromeres creating the kinetochores. Microtubules attach at the kinetochores and the chromosomes begin moving. 81
Metaphase Spindle fibers line the chromosomes along the middle of the cell nucleus. This line is referred to as the metaphase plate. Polar microtubules extend from the pole to the equator, and typically overlap Kinetochore microtubules extend from the pole to the kinetochores This organization helps to ensure that in the next phase, when the chromosomes are separated, each new nucleus will receive one copy of each chromosome 82
Anaphase The paired chromosomes separate at the kinetochores and move to opposite sides of the cell. The chromosomes are pulled by the kinetochore microtubules to the poles and form a "V" shape Motion results from a combination of kinetochore movement along the spindle microtubules and through the physical interaction of polar microtubules. 83
T elophase Chromatids arrive at opposite poles of cell, and new membranes form around the daughter nuclei. The chromosomes disperse and are no longer visible under the light microscope. The spindle fibers disperse, and cytokinesis will start 84
Cytokinesis In animal cells, cytokinesis results when a fiber ring composed of a protein called actin around the center of the cell contracts pinching the cell into two daughter cells, each with one nucleus. In plant cells, synthesis of new cell wall between two daughter cells rather than cleavage furrow in cytoplasm 85
Meiosis Function Reduction division (23 chromosomes per gamete ) Mechanism Each homologue (e.g. “chromosome 7”) replicates to give two sister chromatids Homologues pair (e.g. maternal chromosome 7 and paternal chromosome 7) Exchange of material between non-sister chromatids: crossing-over, recombination Chiasmata (visible cytologically ) are the physical manifestations of crossing-over 86
Meiosis Introduction Meiosis consist s of two successive divisions called the first and the second meiotic divisions 1 st meiotic division Prophase is prolonged Divided into 4 stages 87
Meiosis I Fig A represents leptotene stage-chromosomes become visible consist 2 chromatids , cnt distinguish Fig B represents zygotene stage-pairing of chromosome called synapsis The two chromosomes together c/a bivalent Fig C represents pachytene stage -4 chromatid visible c/a tetrads,2 central and 2 peripheral chromatids. Cont.. 88
Fig D cont. pachytene stage-2 central chromatid cross over c/a crossing over The point of crossing c/a chiasmata Fig E represents Diplotene stage-2 chromosomes of a bivalent try to move apart Exchange of genetic material occur 89
Nuclear membrane disappear Spindle has formed Chromosomes attach to the spindle at equator Chromosome attach by centromere 90
One entire chromosome of the pair moves to either pole NOTE that the centromere does not divide 91
Similar to mitosis NOTE that the chromosome in each cell have been reduced to half the diploid number 92
2 nd mitotic division The 1 st mitotic division is follow by the short interphase There is no duplication of DNA 2 nd meiotic division similar to the mitosis 93
Regulation of cell cycle 94
Nuclear transcription factor Quiescent cell receive a signal to divide MYC protein binds to DNA Transcriptional activation of several growth related genes including cyclin dependent kinases Drive cell into cell cycle MYC decline 95
Cyclins and C yclins –Dependent Kinases Phosphorylation of RB, molecular on off switch G2/M transition initiated by E2F mediated transcription of cycline A,which form complex cycA cdk2 tht regulates mitotic prophase Main mediator tht propel the cell beyond prophase is cyc B-cdk1 complex .activation of complex leds to breakdown of nuclear envelop n initiates mitosis 96
Cell cycle inhibitor 97
cell cycle check points Cell cycle has its own internal control called as checkpoints 2 main check points ,1 at G1/M transition and another at G2/M S phase is point of no return ,before cell makes the final commitment to replicate ,G1/S checkpoint checks for DNA damage DNA damage after its replication can still be repaired as long as the chromatids have not separated .the G2/M checkpoint monitor the completion of DNA replication and checks whether the cell can safely initiates mitosis and separates sister chromatids 98
G1/S checkpoint , cell cycle arrest is mostly mediated through p53,which induce cell cycle inhibitor p21 Arrest of cell cycle by G2/M checkpoints involve the both p53 dependent via cyclin A/cdk-2 and independent via cdc 25 mechanism 99
p53 Also called as “guardian of the genome” Present on chromosome 17 Most mutated gene in human cancer p53 links cell damage with DNA repair ,cell cycle arrest and apoptosis. P53 links cell damage with DNA repair ,cell cycle arrest and apoptosis In reponse to DNA damage,it is phosphorylated by gene that sense the damage and are involved in DNA repair P53 assist in DNA repair by causing G1 arrest and inducing DNA repair A cell with DNA damaged tht cant be repaired is directed by p53 to undergo apoptosis 100
101 Regulation of cell cycle
APOPTOSIS PROGRAMMED CELL DEATH It is a pathway of cell death that is introduced by a tightly regulated suicide program in which cells destined to die activate enzymes that degrade the cell’s own nuclear DNA and nuclear and cytoplasmic proteins. 102
In phisiologic conditions: Normal phenomenon that serves to eliminate cells that are no longer needed and to maintain a steady number of various cell populations in tissues. examples: During embryogenesis. Involution of hormone-dependent tissues upon hormone withdrawal. Cell loss in proliferating cell populations , such as immature lymphocytes in the bone marrow and thymus . 103 causes
In pathological conditions: Eliminates cells that are injured beyond repair without eliciting a host reaction, thus limiting collateral tissue damage. DNA damage: radiation anticancer drugs and hypoxia. Accumulation of mis folded proteins- because of mutations in the genes encoding these proteins or damage caused by free radicals. Viral infections like HIV 104
MECHANISM 105
Regulation 106
Bibliography : (1)Robbins and Cotran : Pathologic basis of disease: seventh edition (2) Gobind Rai Garg Sparsh Gupta :Review of pathology and genetics :fifth edition (3) Inderbir singh :Human Embryology : seventh edition 107