Chapter 3 Lecture Outline 3 1 Copyright c

Chapter 3 Lecture Outline 3 -1 Copyright (c) The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display.

Cellular Form and Function • • Concepts of cellular structure Cell surface Membrane transport Cytoplasm 3 -2

Development of the Cell Theory • cytology – scientific study of cells – began when Robert Hooke coined the word, ‘cellulae’ to describe empty cell walls of cork • Theodor Schwann concluded, about two centuries later, that all animal tissues are made of cells • Louis Pasteur established beyond any reasonable doubt that ‘cells arise only from other cells’ – refuting the idea of spontaneous generation - living things arise from nonliving matter • Modern Cell Theory emerged 3 -3

Modern Cell Theory • All organisms composed of cells and cell products. • Cell is the simplest structural and functional unit of life. – cells are alive • An organism’s structure and functions are due to the activities of its cells. • Cells come only from preexisting cells, not from nonliving matter. – therefore, all life traces its ancestry to the same original cells • Cells of all species have many fundamental similarities in their chemical composition and metabolic mechanisms. 3 -4

Cell Shapes Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Squamous Cuboidal Columnar Polygonal Stellate Spheroid Discoid Fusiform (spindle-shaped) Figure 3. 1 Fibrous 3 -5

Cell Shapes • about 200 types of cells in the human body • Squamous - thin and flat with nucleus creating bulge • Polygonal - irregularly angular shapes with 4 or more sides • Stellate – starlike shape • Cuboidal – squarish and about as tall as they are wide • Columnar - taller than wide • Spheroid to Ovoid – round to oval • Discoid - disc-shaped • Fusiform - thick in middle, tapered toward the ends • Fibrous – threadlike shape • Note: some of these shapes are cell appearance in tissue sections, but not their 3 dimensional shape 3 -6

Cell Size • Human cell size – most from 10 - 15 micrometers (µm) in diameter • egg cells (very large)100 µm diameter – barely visible to the naked eye • nerve cell at 1 meter long – longest human cell – too slender to be seen with naked eye • Limitations on cell size – cell growth increases volume more than surface area – surface area of a cell is proportional to the square of its diameter – volume of a cell is proportional to the cube of its diameter • nutrient absorption and waste removal utilize surface area – if cell becomes too large, may rupture like overfilled water balloon 3 -7

Cell Surface Area and Volume Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. 20 mm Growth 20 mm Figure 3. 2 10 mm Large cell Diameter = 20 mm Surface area = 20 mm ´ 6 = 2, 400 mm 2 Volume = 20 mm ´ 20 mm = 8, 000 mm 3 Small cell Diameter = 10 mm Surface area = 10 mm ´ 6 = 600 mm 2 Volume = 10 mm ´ 10 mm = 1, 000 mm 3 Effect of cell growth: Diameter (D) increased by a factor of 2 Surface area increased by a factor of 4 (= D 2) Volume increased by a factor of 8 (= D 3) 3 -8

General Cell Structure • Light microscope reveals plasma membrane, nucleus and cytoplasm – fluid between the nucleus and surface membrane • Resolution (ability to reveal detail) of electron microscopes reveals ultrastructure – organelles, cytoskeleton and cytosol (ICF) Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Plasma membrane Nucleus Figure 3. 3 Nuclear envelope Mitochondria Golgi vesicle Golgi complex Ribosomes 3 -9 2. 0 µm © K. G. Muri/Visuals Unlimited

Magnification versus Resolution Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. (a) Light microscope (LM) From Cell Ultrastructure by William A. Jensen and Roderick B. Park. © 1967 by Wadsworth Publishing Co. , Inc. Reprinted by permission of the publisher Figure 3. 4 a Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. (b) Transmission electron microscope (TEM) 2. 0 µm From Cell Ultrastructure by William A. Jensen and Roderick B. Park. © 1967 by Wadsworth Publishing Co. , Inc. Reprinted by permission of the publisher Figure 3. 4 b • Magnification of 750 x seen through both light and transmission electron microscope • Increased resolution reveals the finer details 3 -10

Magnification versus Resolution 3 -11

Major Constituents of Cell • plasma (cell) membrane – surrounds cell – made of proteins and lipids – composition and function can vary from one region of the cell to another Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Apical cell surface Microfilaments Microvillus • cytoplasm – organelles – cytoskeleton – cytosol (intracellular fluid - ICF) Terminal web Desmosome Secretory vesicle undergoing exocytosis Fat droplet Secretory vesicle Intercellular space Centrosome Centrioles Golgi vesicles Golgi complex Lateral cell surface Free ribosomes Intermediate filament Nucleus Lysosome Nucleolus Microtubule Nuclear envelope Rough endoplasmic reticulum Smooth endoplasmic reticulum Mitochondrion Plasma membranes Hemidesmosome • extracellular fluid – ECF – fluid outside of cell Basal cell surface Figure 3. 5 Basement membrane 3 -12

Plasma Membrane unit membrane – forms the border of the cell and many of its organelles -appears as a pair of dark parallel lines around cell (viewed with the electron microscope) plasma membrane – unit membrane at cell surface -defines cell boundaries Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Plasma membrane of upper cell -governs interactions with other cells Intercellular space Plasma membrane of lower cell -controls passage of materials in and out of cell -intracellular face – side that faces cytoplasm -extracellular face – side that faces outward Nuclear envelope Nucleus (a) 100 nm a: © Don Fawcett/Photo Researchers, Inc. Figure 3. 6 a 3 -13

Plasma Membrane Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Extracellular fluid Peripheral protein Glycolipid Glycoprotein Carbohydrate chains Extracellular face of membrane Phospholipid bilayer Channel Peripheral protein Cholesterol Transmembrane protein Intracellular fluid Proteins of cytoskeleton Intracellular face of membrane Figure 3. 6 b (b) • Oily film of lipids with diverse proteins embedded 3 -14

Membrane Lipids • 98% of molecules in plasma membrane are lipids • Phospholipids – – – 75% of membrane lipids are phospholipids amphiphilic molecules arranged in a bilayer hydrophilic phosphate heads face water on each side of membrane hydrophobic tails – directed toward the center, avoiding water drift laterally from place to place movement keeps membrane fluid • Cholesterol – 20% of the membrane lipids – holds phospholipids still and can stiffen membrane • Glycolipids – 5% of the membrane lipids – phospholipids with short carbohydrate chains on extracellular face – contributes to glycocalyx – carbohydrate coating on the 3 -15 cells surface

Membrane Proteins • Membrane proteins – 2% of the molecules in plasma membrane – 50% of its weight • Transmembrane proteins – pass through membrane – have hydrophilic regions in contact with cytoplasm and extracellular fluid – have hydrophobic regions that pass back and forth through the lipid of the membrane – most are glycoproteins – can drift about freely in phospholipid film – some anchored to cytoskeleton Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Transmembrane protein: • Peripheral proteins – adhere to one face of the membrane – usually tethered to the cytoskeleton Figure 3. 7 3 -16

Membrane Protein Functions • receptors, second-messenger systems, enzymes, ion channels, carriers, cell-identity markers, cell-adhesion molecules Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Chemical messenger Breakdown products Ions (a) Receptor A receptor that binds to chemical messengers such as hormones sent by other cells (b) Enzyme An enzyme that breaks down a chemical messenger and terminates its effect (c) Ion Channel A channel protein that is constantly open and allows ions to pass into and out of the cell CAM of another cell (d) Gated ion channel A gated channel that opens and closes to allow ions through only at certain times Figure 3. 8 (e) Cell-identity marker A glycoprotein acting as a cellidentity marker distinguishing the body’s own cells from foreign cells (f) Cell-adhesion molecule (CAM) A cell-adhesion molecule (CAM) that binds one cell to another 3 -17

Membrane Receptors • Cell communication via chemical signals – receptors – surface proteins on plasma membrane of target cell – bind these chemicals (hormones, neurotransmitters) – receptor usually specific for one substrate 3 -18

Second Messenger System Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. 1 A messenger such as epinephrine (red triangle) binds to a receptor in the plasma membrane. First messenger Receptor G 2 The receptor releases a G protein, which then travels freely in the cytoplasm and can go on to step 3 or have various other effects on the cell. Adenylate cyclase G ATP Pi Pi 3 The G protein binds to an enzyme, adenylate cyclase, in the plasma membrane. Adenylate cyclase c. AMP converts ATP to cyclic (second AMP (c. AMP), the messenger) second messenger. 4 c. AMP activates a cytoplasmic enzyme called a kinase. Inactive kinase Activated kinase Inactive enzymes Figure 3. 9 Pi 5 Kinases add phosphate groups (Pi) to other cytoplasmic enzymes. This activates some enzymes and deactivates others, leading to varied metabolic effects in the cell. Activated enzymes Various metabolic effects 3 -19

Second Messenger System • Chemical first messenger (epinephrine) binds to a surface receptor – triggers changes within the cell that produces a second messenger in the cytoplasm • Receptor activates G protein – an intracellular peripheral protein – guanosine triphosphate (GTP) an ATP like compound • G protein relays signal to adenylate cyclase which converts ATP to c. AMP (2 nd messenger) • c. AMP activates a kinase in the cytosol • Kinases add phosphate groups to other cellular enzymes – activates some enzymes, and inactivates others triggering a wide variety of physiological changes in cells • Up to 60% of modern drugs work by altering activity of G proteins. 3 -20

Membrane Enzymes • enzymes in plasma membrane carry out final stages of starch and protein digestion in small intestine • help produce second messengers (c. AMP) • break down chemical messengers and hormones whose job is done – stops excessive stimulation 3 -21

Ion Channels • Transmembrane proteins with pores that allow water and dissolved ions to pass through membrane – some constantly open – some are gated-channels that open and close in response to stimuli • ligand (chemically)-regulated gates • voltage-regulated gates • mechanically regulated gates (stretch and pressure) • play an important role in the timing of nerve signals and muscle contraction 3 -22

Membrane Carriers or Pumps • Transmembrane proteins bind to glucose, electrolytes, and other solutes – transfer them across membrane • Pumps consume ATP in the process 3 -23

Cell-Identity Markers • Glycoproteins contribute to the glycocalyx – carbohydrate surface coating – acts like a cell’s ‘identification tag’ • Enables our bodies to identify which cells belong to it and which are foreign invaders 3 -24

Cell-Adhesion Molecules • Adhere cells to each other and to extracellular material • cells do not grow or survive normally unless they are mechanically linked to the extracellular material 3 -25

Glycocalyx • Unique fuzzy coat external to the plasma membrane – carbohydrate moieties of membrane glycoproteins and glycolipids – unique in everyone, but identical twins • Functions (see Table 3. 2) – – protection immunity to infection defense against cancer transplant compatibility - cell adhesion - fertilization - embryonic development 3 -26

Microvilli • Extensions of membrane (1 -2 m) – serves to increase cell’s surface area – best developed in cells specialized in absorption – gives 15 – 40 times more absorptive surface area • on some cells they are very dense and appear as a fringe – “brush border” – milking action of actin • actin filaments shorten microvilli – pushing absorbed contents down into cell 3 -27

Microvilli Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Glycocalyx Microvillus Actin microfilaments (a) Figure 3. 10 a 1. 0 µm (b) a: © Ed Reschke; b: Biophoto Associates/Photo Researchers, Inc. 0. 1 µm Figure 3. 10 b Actin microfilaments are found in center of each microvilli. 3 -28

Structure of Cilia Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Cilia (a) Custom Medical Stock Photo, Inc. Figure 3. 11 a 10 m 3 -29

Cilia • Hairlike processes 7 -10 m long – single, nonmotile primary cilium found on nearly every cell – “antenna’ for monitoring nearby conditions – sensory in inner ear, retina, nasal cavity, and kidney • Motile cilia – respiratory tract, uterine tubes, ventricles of the brain, efferent ductules of testes – beat in waves – sweep substances across surface in same direction – power strokes followed by recovery strokes Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Mucus Saline layer Epithelial cells 1 2 3 Power stroke (a) Figure 3. 12 a (b) 4 5 6 7 Recovery stroke Figure 3. 12 b 3 -30

Cross Section of a Cilium Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. • Axoneme - core of cilia that is the structural basis for ciliary movement Axoneme: Peripheral microtubules Central microtubules Dynein arms Shaft of cilium • has 9 + 2 structure of microtubules Basal body Plasma membrane (b) – 9 pairs form basal body inside the cell membrane Dynein arm Central microtubule • anchors cilium Axoneme Figure 3. 11 b, d Peripheral microtubules (d) – dynein arms “crawls” up adjacent microtubule bending the cilia Cilia • uses energy from ATP • Saline Layer – chloride pumps pump Cl- into ECF – Na+ and H 2 O follows – cilia beat freely in saline layer Microvilli Dynein arm Central microtubule Peripheral microtubules (c) 0. 15 µm c: © Biophoto Associates/Photo Researchers, Inc. Figure 3. 11 c 3 -31

Cilia & Cystic Fibrosis • Saline layer at cell surface due to chloride pumps move Cl- out of cell. Na+ ions and H 2 O follow Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Mucus • Cystic fibrosis – hereditary disease in which cells make chloride pumps, but fail to install them in the plasma membrane Saline layer Epithelial cells – chloride pumps fail to create adequate saline layer on cell surface (a) Figure 3. 12 a • thick mucus plugs pancreatic ducts and respiratory tract – inadequate digestion of nutrients and absorption of oxygen – chronic respiratory infections – life expectancy of 30 3 -32

Flagella • tail of the sperm - only functional flagellum • whiplike structure with axoneme identical to cilium – much longer than cilium – stiffened by coarse fibers that supports the tail • movement is more undulating, snakelike – no power stroke or recovery stroke as in cilia 3 -33

Membrane Transport • plasma membrane – a barrier and a gateway between the cytoplasm and ECF – selectively permeable – allows some things through, and prevents other things from entering and leaving the cell • passive transport mechanisms requires no ATP – random molecular motion of particles provides the necessary energy – filtration, diffusion, osmosis • active transport mechanisms consumes ATP – active transport and vesicular transport • carrier-mediated mechanisms use a membrane protein to transport substances from one side of the membrane to the 3 -34 other

Filtration • Filtration - process in which particles are driven through Solute a selectively permeable membrane by hydrostatic Water Capillary wall pressure (force exerted blood on a membrane by water) Red cell Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. • Examples – filtration of nutrients through gaps in blood capillary walls into tissue fluids Blood pressure in capillary forces water and small solutes such as salts through narrow clefts between capillary cells. Clefts hold back larger particles such as red blood cells. Figure 3. 13 – filtration of wastes from the blood in the kidneys while holding back blood cells and proteins 3 -35

Simple Diffusion • Simple Diffusion – the net movement of particles from area of high concentration to area of low concentration Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. – due to their constant, spontaneous motion • Also known as movement down the concentration gradient – concentration of a substance differs from one point to another Down gradient Up gradient Figure 3. 14 3 -36

Diffusion Rates • Factors affecting diffusion rate through a membrane – temperature - temp. , motion of particles – molecular weight - larger molecules move slower – steepness of concentrated gradient - difference, rate – membrane surface area - area, rate – membrane permeability - permeability, rate 3 -37

Membrane Permeability • Diffusion through lipid bilayer – Nonpolar, hydrophobic, lipid-soluble substances diffuse through lipid layer • Diffusion through channel proteins – water and charged, hydrophilic solutes diffuse through channel proteins in membrane • Cells control permeability by regulating number of channel proteins or by opening and closing gates 3 -38

Osmosis • Osmosis - flow of water from one side of a selectively permeable membrane to the other – from side with higher water concentration to the side with lower water concentration – reversible attraction of water to solute particles forms hydration spheres – makes those water molecules less available to diffuse back to the side from which they came Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Side A Side B (a) Start Figure 3. 15 a • Aquaporins - channel proteins specialized for passage of water 3 -39

Aquaporins • Aquaporins - channel proteins in plasma membrane specialized for passage of water Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Side A Side B – cells can increase the rate of osmosis by installing more aquaporins – decrease rate by removing them • Significant amounts of water diffuse even through the hydrophobic, phospholipid regions of the plasma membrane (a) Start Figure 3. 15 a 3 -40

Osmotic Pressure • Osmotic Pressure amount of hydrostatic pressure required to stop osmosis Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Osmotic pressure Hydrostatic pressure • Osmosis slows due to hydrostatic pressure • Heart drives water out of capillaries by reverse osmosis – capillary filtration (b) 30 minutes later Figure 3. 15 b 3 -41

Osmolarity • One osmole - 1 mole of dissolved particles – 1 M Na. Cl (1 mole Na+ ions + 1 mole Cl- ions) thus 1 M Na. Cl = 2 osm/L • Osmolarity – number of osmoles of solute per liter of solution • Osmolality – number of osmoles of solute per kilogram of water • Physiological solutions are expressed in milliosmoles per liter (m. Osm/L) – blood plasma = 300 m. Osm/L – osmolality similar to osmolarity at concentration of body fluids – less than 1% difference 3 -42

Tonicity • Tonicity - ability of a solution to affect fluid volume and pressure in a cell – depends on concentration and permeability of solute • Hypotonic solution – has a lower concentration of nonpermeating solutes than intracellular fluid (ICF) • high water concentration – cells absorb water, swell and may burst (lyse) • Hypertonic solution – has a higher concentration of nonpermeating solutes • low water concentration – cells lose water + shrivel (crenate) • Isotonic solution – concentrations in cell and ICF are the same – cause no changes in cell volume or cell shape – normal saline 3 -43

Effects of Tonicity on RBCs Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. (a) Hypotonic (b) Isotonic (c) Hypertonic © Dr. David M. Phillips/Visuals Unlimited Figure 3. 16 a Figure 3. 16 b Figure 3. 16 c Hypotonic, isotonic and hypertonic solutions affect the fluid volume of a red blood cell. Notice the crenated and swollen cells. 3 -44

Carrier-Mediated Transport • Transport proteins in the plasma membrane that carry solutes from one side of the membrane to the other • Specificity: – transport proteins specific for a certain ligand – solute binds to a specific receptor site on carrier protein – differs from membrane enzymes because carriers do not chemically change their ligand • simply picks them up on one side of the membrane, and release them, unchanged, on the other • Saturation: – as the solute concentration rises, the rate of transport rises, but only to a point – Transport Maximum (Tm) • 2 types of carrier mediated transport – facilitated diffusion and active transport 3 -45

Membrane Carrier Saturation Rate of solute transport (molecules/sec passing through plasma membrane) Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Transport maximum (Tm) Figure 3. 17 Concentration of solute • Transport maximum - transport rate when all carriers are occupied 3 -46

Membrane Carriers • Uniport – carries only one solute at a time • Symport – carries 2 or more solutes simultaneously in same direction (cotransport) • Antiport – carries 2 or more solutes in opposite directions (countertransport) – sodium-potassium pump brings in K+ and removes Na+ from cell • carriers employ two methods of transport – facilitated diffusion – active transport 3 -47

Facilitated Diffusion • facilitated diffusion - carrier-mediated transport of solute through a membrane down its concentration gradient • does not consume ATP • solute attaches to binding site on carrier, carrier changes confirmation, then releases solute on other side of membrane Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. ECF Figure 3. 18 ICF 1 A solute particle enters the channel of a membrane protein (carrier). 2 The solute binds to a receptor site on the carrier and the carrier changes conformation. 3 The carrier releases the solute on the other side of the membrane. 3 -48

Active Transport • active transport – carrier-mediated transport of solute through a membrane up (against) its concentration gradient • ATP energy consumed to change carrier • Examples of uses: – sodium-potassium pump keeps K+ concentration higher inside the cell – bring amino acids into cell – pump Ca 2+ out of cell 3 -49

Sodium-Potassium Pump • each pump cycle consumes one ATP and exchanges three Na+ for two K+ • keeps the K+ concentration higher and the Na+ concentration lower with in the cell than in ECF Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. • necessary because Na+ and K+ constantly leak through membrane 3 Na+ out Extracellular fluid – half of daily calories utilized for Na+ - K+ pump Figure 3. 19 ATP ADP + Pi Intracellular fluid 2 K+ in 3 -50

Functions of + Na + -K Pump • Regulation of cell volume – “fixed anions” attract cations causing osmosis – cell swelling stimulates the Na+- K+ pump to ion concentration, osmolarity and cell swelling • Secondary active transport – steep concentration gradient maintained between one side of the membrane and the other – (water behind a dam) – Sodium-glucose transport protein (SGLT) – simultaneously binds Na+ and glucose and carries both into the cell – does not consume ATP • Heat production – thyroid hormone increase # of Na+ - K+ pumps – consume ATP and produce heat as a by-product • Maintenance of a membrane potential in all cells – pump keeps inside more negative, outside more positive – necessary for nerve and muscle function 3 -51

Vesicular Transport • Vesicular Transport – processes that move large particles, fluid droplets, or numerous molecules at once through the membrane in vesicles – bubblelike enclosures of membrane – motor proteins consumes ATP • Endocytosis –vesicular processes that bring material into the cell – phagocytosis – “cell eating” - engulfing large particles • pseudopods phagosomes macrophages – pinocytosis – “cell drinking” taking in droplets of ECF containing molecules useful in the cell • pinocytic vesicle – receptor-mediated endocytosis – particles bind to specific receptors on plasma membrane • clathrin-coated vesicle • Exocytosis – discharging material from the cell • Utilizes motor proteins energized by ATP 3 -52

Phagocytosis or “Cell-Eating” Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Particle 7 The indigestible residue is voided by exocytosis. 1 A phagocytic cell encounters a particle of foreign matter. Pseudopod Residue 2 The cell surrounds the particle with its pseudopods. Nucleus Phagosome 6 The phagolysosome fuses with the plasma membrane. Lysosome Vesicle fusing with membrane 3 The particle is phagocytized and contained in a phagosome. Phagolysosome 5 Enzymes from the lysosome digest the foreign matter. 4 The phagosome fuses with a lysosome and becomes a phagolysosome. Figure 3. 21 3 -53 Keeps tissues free of debris and infectious microorganisms.

Pinocytosis or “Cell-Drinking” • Taking in droplets of ECF – occurs in all human cells • Membrane caves in, then pinches off into the cytoplasm as pinocytotic vesicle 3 -54

Receptor Mediated Endocytosis Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Extracellular molecules Receptor Coated pit Clathrin 1 Extracellular molecules bind to receptors on plasma membrane; receptors cluster together. 2 Plasma membrane sinks inward, forms clathrin-coated pit. Clathrincoated vesicle 3 Pit separates from plasma membrane, forms clathrin-coated vesicle containing concentrated molecules from ECF. (all): Company of Biologists, Ltd. Figure 3. 22 (1, 2 and 3) 3 -55

Receptor Mediated Endocytosis • more selective endocytosis • enables cells to take in specific molecules that bind to extracellular receptors • Clathrin-coated vesicle in cytoplasm – uptake of LDL from bloodstream 3 -56

Transcytosis Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Capillary endothelial cell Intercellular cleft Capillary lumen Pinocytotic vesicles Muscle cell Figure 3. 23 Tissue fluid 0. 25 µm © Don Fawcett/Photo Researchers, Inc. • Transport of material across the cell by capturing it on one side and releasing it on the other • Receptor-mediated endocytosis moves it into cell and exocytosis moves it out the other side – insulin 3 -57

Exocytosis • Secreting material • replacement of plasma membrane removed by endocytosis Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Dimple Fusion pore Secretion Plasma membrane Linking protein Secretory vesicle (a) (b) 1 A secretory vesicle approaches 2 The plasma membrane and vesicle unite to form a fusion the plasma membrane and docks pore through which the vesicle on it by means of linking proteins. contents are released. The plasma membrane caves in at that point to meet the vesicle. Courtesy of Dr. Birgit Satir, Albert Einstein College of Medicine Figure 3. 24 a, b 3 -58

The Cell Interior • structures in the cytoplasm – organelles, cytoskeleton, and inclusions – all embedded in a clear gelatinous cytosol • Organelles – internal structures of a cell that carry out specialized metabolic tasks – membranous organelles – those surrounded by one or two layers of unit membrane • nucleus, mitochondria, lysosome, peroxisome, endoplasmic reticulum, and Golgi complex – organelles not surrounded by membranes • ribosome, centriole, basal bodies • Cytoskeleton – collection of protein filaments – microfilaments, intermediate filaments, and microtubules • Inclusions – stored cellular components and fat droplets 3 -59

Nucleus • Largest organelle (5 m in diameter) – most cells have one nucleus – a few cells are anuclear or multinucleate • nuclear envelope - two unit membranes surround nucleus – perforated by nuclear pores formed by rings of protein • regulate molecular traffic through envelope • hold two unit membranes together – supported by nuclear lamina • • web of protein filaments supports nuclear envelope and pores provides points of attachment and organization for chromatin plays role in regulation of the cell life cycle • nucleoplasm – material in nucleus – chromatin (thread-like matter) composed of DNA and protein – nucleoli – one or more dark masses where ribosomes are produced 3 -60

Micrograph of The Nucleus Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Nuclear pores Nucleolus Nucleoplasm Nuclear envelope (a) Interior of nucleus 2 mm (b) Surface of nucleus 1. 5 mm a: © Richard Chao; b: © E. G. Pollock Figure 3. 25 a Figure 3. 25 b 3 -61

Endoplasmic Reticulum • endoplasmic reticulum - system of interconnected channels called cisternae enclosed by unit membrane • rough endoplasmic reticulum – composed of parallel, flattened sacs covered with ribosomes – continuous with outer membrane of nuclear envelope – adjacent cisternae are often connected by perpendicular bridges – produces the phospholipids and proteins of the plasma membrane – synthesizes proteins that are packaged in other organelles or secreted from cell 3 -62

Endoplasmic Reticulum • smooth endoplasmic reticulum – lack ribosomes – cisternae more tubular and branching – cisternae are thought to be continuous with those of rough ER – synthesizes steroids and other lipids – detoxifies alcohol and other drugs – manufactures all membranes of the cell • rough and smooth ER are functionally different parts of the same network 3 -63

Smooth and Rough ER Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Rough endoplasmic reticulum Ribosomes Cisternae (c) Smooth endoplasmic reticulum Figure 3. 26 c 3 -64

Endoplasmic Reticulum Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Cisternae of rough ER Oil droplet (inclusion) Nucleus Ribosomes of rough ER Smooth endoplasmic reticulum (a) 1 µm (b) 1 µm © Don Fawcett/Photo Researchers, Inc. Figure 3. 26 a Figure 3. 26 b 3 -65

Ribosomes • Ribosomes - small granules of protein and RNA – found in nucleoli, in cytosol, and on outer surfaces of rough ER, and nuclear envelope • they ‘read’ coded genetic messages (messenger RNA) and assemble amino acids into proteins specified by the code 3 -66

Golgi Complex • Golgi complex - a small system of cisternae that synthesize carbohydrates and put the finishing touches on protein and glycoprotein synthesis – receives newly synthesized proteins from rough ER – sorts them, cuts and splices some of them, adds carbohydrate moieties to some, and packages the protein into membrane-bound Golgi vesicles • some become lysosomes • some migrate to plasma membrane and fuse to it • some become secretory vesicles for later release 3 -67

Golgi Complex Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Golgi vesicles Golgi complex Figure 3. 27 Visuals Unlimited 600 nm 3 -68

Lysosomes • Lysosomes - package of enzymes bound by a single unit membrane – extremely variable in shape • Functions – intracellular hydrolytic digestion of proteins, nucleic acids, complex carbohydrates, phospholipids, and other substances – autophagy – digest and dispose of worn out mitochondria and other organelles – autolysis – ‘cell suicide’ – some cells are meant to do a certain job and then destroy themselves 3 -69

Lysosomes and Peroxisomes Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Mitochondria Peroxisomes Lysosomes Smooth ER Golgi complex (a) Lysosomes 1 mm (b) Peroxisomes 0. 3 mm © Don Fawcett/Photo Researchers, Inc. Figure 3. 28 a Figure 3. 28 b 3 -70

Peroxisomes • Peroxisomes - resemble lysosomes but contain different enzymes and are not produced by the Golgi complex • General function is to use molecular oxygen to oxidize organic molecules – these reactions produce hydrogen peroxide (H 2 O 2) – catalase breaks down excess peroxide to H 2 O and O 2 – neutralize free radicals, detoxify alcohol, other drugs, and a variety of blood-borne toxins – breakdown fatty acids into acetyl groups for mitochondrial use in ATP synthesis • In all cells, but abundant in liver and kidney 3 -71

Mitochondrion • mitochondria – organelles specialized for synthesizing ATP Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. • variety of shapes – spheroid, rodshaped, kidney bean-shaped, or threadlike • surrounded by a double unit membrane – inner membrane has folds called cristae – spaces between cristae are called matrix • matrix contains ribosomes, enzymes used for ATP synthesis, small circular DNA molecule – mitochondrial DNA (mt. DNA) • “Powerhouses” of the cell – energy is extracted from organic molecules and transferred to ATP Matrix Outer membrane Inner membrane Mitochondrial ribosome Intermembrane space Crista Figure 3. 29 b 3 -72

Mitochondrion Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Matrix Outer membrane Inner membrane Mitochondrial ribosome Figure 3. 29 a, b Intermembrane space Crista 1 µm 3 -73 (Left): Dr. Donald Fawcett & Dr. Porter/Visuals Unlimited

Evolution of Mitochondrion • It is a virtual certainty that mitochondria evolved from bacteria that invaded another primitive cell, survived in the cytoplasm, and became permanent residents – its two unit membranes suggests that the original bacterium provided the inner membrane, and the host cell’s phagosome provided the outer membrane – mitochondrial ribosomes more like bacterial ribosomes – has its own mt. DNA • small circular molecule resembling bacterial DNA • replicates independently of nuclear DNA – when a sperm fertilizes the egg, any mitochondria introduced by the sperm are usually destroyed, and only those provided by the egg are passed on to the developing embryo • mitochondrial DNA is almost exclusively inherited through the mother – mutates more readily than nuclear DNA • no mechanism for DNA repair • produces rare hereditary diseases • mitochondrial myopathy , mitochondrial encephalomyopathy, and others 3 -74

Centrioles • centriole – a short cylindrical assembly of microtubules arranged in nine groups of three microtubules each • two centrioles lie perpendicular to each other within a small clear area of cytoplasm - centrosome – play role in cell division • cilia and flagella formation – each basal body of a cilium or flagellum is a single centriole oriented perpendicular to plasma membrane – basal bodies originate in centriolar organizing center • migrates to plasma membrane – two microtubules of each triplet elongate to form the nine pairs of peripheral microtubules of the axoneme 3 -75 – cilium reaches full length in less than one hour

Centrioles Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Figure 3. 30 a, b Microtubules Protein link Longitudinal view Cross section 0. 1 µm (a) Cross-section (TEM) Microtubules (b) Pair of centrioles 3 -76 a: From: Manley Mc. Gill, D. P. Highfield, T. M. Monahan, and B. R. Brinkley Effects of Nucleic Acid Specific Dyes on Centrioles of Mammalian Cells, published in the Journal of Ultrastructure Research 57, 43 -53 (1976), pg. 48, fig. 6, with permission from Elsevier

Cytoskeleton • Cytoskeleton - collection of filaments and cylinders – determines shape of cell, lends structural support, organizes its contents, directs movement of substances through the cell, and contributes to the movements of cell as a whole. • Composed of: – microfilaments – made of protein actin • form network on cytoplasmic side of plasma membrane called the terminal web (membrane skeleton) – provides physical support for phospholipid bilayer – actin supports microvilli and produces cell movements – intermediate fibers – thicker and stiffer than microfilaments • resist stresses placed on cell • participate in junctions that attach some cells to their neighbors • line nuclear envelope and form cagelike nuclear lamina that encloses DNA – microtubules – cylinders made of 13 parallel strands called protofilaments 3 -77

Microtubules • a microtubule is a cylinder of 13 parallel strands called protofilaments – each protofilament is a long chain of globular proteins called tubulin • microtubules radiate from centrosome and hold organelles in place, form bundles that maintain cell shape and rigidity, and act somewhat like railroad tracks – motor proteins ‘walk’ along these tracks carrying organelles and other macromolecules to specific locations in the cell • not permanent structures, they come and go moment by moment Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. (a) (b) (c) Microtubule Protofilaments Dynein arms Tubulin Figure 3. 32 3 -78

Cytoskeleton Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. Microvilli Microfilaments Terminal web Secretory vesicle in transport Desmosome Lysosome Kinesin Microtubule Intermediate filaments Microtubule in the process of assembly Centrosome Microtubule undergoing disassembly Nucleus Mitochondrion (a) Basement membrane Hemidesmosome Figure 3. 31 a 3 -79

EM and Fluorescent Antibodies demonstrate Cytoskeleton Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. (b) © K. G. Murti/Visuals Unlimited Figure 3. 31 b 15 µm 3 -80

Inclusions • two kinds of inclusions – Stored cellular products • glycogen granules, pigments and fat droplets – Foreign bodies • viruses, intracellular bacteria, and dust particles and other debris phagocytized by cell • never enclosed in a unit membrane • not essential for cell survival 3 -81

Table 3. 4 • Summary of organelles: their appearance and function 3 -82