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Chapter 3 *Lecture PowerPoint Cellular Form and Function *See separate FlexArt PowerPoint slides for all figures and tables preinserted into PowerPoint without notes. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Introduction • All organisms are composed of cells – Single-cell organisms humans • Cells are responsible for all structural and functional properties of a living organism – Workings of the human body – Mechanisms of disease – Rationale of therapy 2-2 Concepts of Cellular Structure • Expected Learning Outcomes – Discuss the development and modern tenets of the cell theory. – Describe cell shapes from their descriptive terms. – State the size range of human cells and discuss factors that limit their size. – Discuss the way that developments in microscopy have changed our view of cell structure. – Outline the major components of a cell. 2-3 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‖ – Refutes the idea of spontaneous generation—living things arise from nonliving matter 3-4 Development of the Cell Theory • Modern cell theory – All organisms composed of cells and cell products – The cell is the simplest structural and functional unit of life – An organism’s structure and functions are due to the activities of its cells – Cells come only from preexisting cells, not from nonliving matter – Cells of all species have many fundamental similarities in their chemical composition and metabolic mechanisms. 3-5 Cell Shapes and Sizes • About 200 types of cells in the human body • Squamous—thin and flat with nucleus creating bulge • Polygonal—irregularly angular shapes with four or more sides • Stellate—starlike shape • Cuboidal—squarish and about as tall as is 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 cell shapes appear as in tissue sections, but not their three-dimensional shape 3-6 Cell Shapes and Sizes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Squamous Cuboidal Columnar Polygonal Stellate Spheroid Discoid Fusiform (spindle-shaped) Figure 3.1 Fibrous 3-7 Cell Shapes and Sizes • 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 3-8 Cell Shapes and Sizes • 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 3-9 Cell Shapes and Sizes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 20 m Growth 20 m Figure 3.2 10 m 10 m Large cell Diameter = 20 mm Surface area = 20 mm 20 mm 6 = 2,400 mm2 Volume = 20 mm 20 mm 20 mm = 8,000 mm3 Small cell Diameter = 10 mm Surface area = 10 mm 10 mm 6 = 600 mm2 Volume = 10 mm 10 mm 10 mm = 1,000 mm3 Effect of cell growth: Diameter (D) increased by a factor of 2 Surface area increased by a factor of 4 (= D2) Volume increased by a factor of 8 (= D3) 3-10 Basic Components of a Cell • Light microscope reveals plasma membrane, nucleus, and cytoplasm – 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 McGraw-Hill Companies, Inc. Permission required for reproduction or display. Plasma membrane Nucleus Nuclear envelope Figure 3.3 Mitochondria Golgi vesicle Golgi complex Ribosomes 2.0 © K.G. Muri/Visuals Unlimited m 3-11 Basic Components of a Cell Copyright © The McGraw-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 3.4a Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (b) Transmission electron microscope (TEM) 2.0 m From Cell Ultrastructure by William A. Jensen and Roderick B. Park. © 1967 by Wadsworth Publishing Co., Inc. Reprinted by permission of the publisher Figure 3.4b • Magnification of x750 seen through both light and transmission electron microscopes • Increased resolution reveals the finer details 3-12 Basic Components of a Cell 3-13 Basic Components of a Cell • Plasma (cell) membrane – Surrounds cell, defines boundaries – Made of proteins and lipids – Composition and function can vary from one region of the cell to another Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Cytoplasm – Organelles – Cytoskeleton – Cytosol (intracellular fluid, ICF) Apical cell surface Microfilaments Microvillus 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 • Extracellular fluid (ECF) – Fluid outside of cell Mitochondrion Plasma membranes Hemidesmosome Basal cell surface Figure 3.5 Basement membrane 3-14 The Cell Surface • Expected Learning Outcomes – Describe the structure of the plasma membrane. – Explain the functions of the lipid, protein, and carbohydrate components of the plasma membrane. – Describe a second-messenger system and discuss its importance in human physiology. – Describe the composition and functions of the glycocalyx that coats cell surfaces. – Describe the structure and functions of microvilli, cilia, and flagella. 3-15 The 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 - Governs interactions with other cells - Controls passage of materials in and out of cell - Intracellular face—side that faces cytoplasm - Extracellular face—side that faces outward Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Plasma membrane of upper cell Intercellular space Plasma membrane of lower cell Nuclear envelope Nucleus (a) 100 nm © Don Fawcett/Photo Researchers, Inc. Figure 3.6a The Plasma Membrane Copyright © The McGraw-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 3.6b (b) • Oily film of lipids with diverse proteins embedded 3-17 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 3-18 Membrane Lipids • 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 cell surface 3-19 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 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Carbohydrate Transmembrane protein: Hydrophilic region Hydrophobic region Phospholipid bilayer Cytoskeletal protein Anchoring peripheral protein Figure 3.7 3-20 Membrane Proteins Cont. – Most are glycoproteins – Can drift about freely in phospholipid film – Some anchored to cytoskeleton • Peripheral proteins – Adhere to one face of the membrane – Usually tethered to the cytoskeleton Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Carbohydrate Transmembrane protein: Hydrophilic region Hydrophobic region Phospholipid bilayer Cytoskeletal protein Anchoring peripheral protein Figure 3.7 3-21 Membrane Proteins • Functions of membrane proteins include the following: – Receptors, second-messenger systems, enzymes, ion channels, carriers, cell-identity markers, cell-adhesion molecules Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemical messenger Breakdown products CAM of another cell 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 (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 3-22 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 3-23 Second-Messenger Systems • Messenger (chemical) binds to a surface receptor • Triggers changes within the cell that produce a second messenger in the cytoplasm – Involves transmembrane proteins and peripheral proteins 3-24 Enzymes • Enzymes in plasma membrane carry out final stages of starch and protein digestion in small intestine • Help produce second messengers (cAMP) • Break down chemical messengers and hormones whose job is done – Stops excessive stimulation 3-25 Channel Proteins • Transmembrane proteins with pores that allow water and dissolved ions to pass through membrane – Some are 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 • Channelopathies—family of diseases that result from defects in channel proteins 3-26 Carriers or Pumps • Transmembrane proteins bind to glucose, electrolytes, and other solutes – Transfer them across membrane • Pumps consume ATP in the process 3-27 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 3-28 Cell-Adhesion Molecules (CAMs) • 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 – Special events: sperm–egg binding; binding of immune cell to a cancer cell requires CAMs 3-29 Second Messengers • 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 cAMP (second messenger) 3-30 Second Messengers • cAMP 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 3-31 Second Messenger System Copyright © The McGraw-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 Adenylate cyclase G Pi 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. ATP Pi 3 The G protein binds to an enzyme, adenylate cyclase, in the plasma membrane. Adenylate cyclase cAMP converts ATP to cyclic (second AMP (cAMP), the messenger) second messenger. 4 cAMP 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 3-32 The Glycocalyx • Unique fuzzy coat external to the plasma membrane – Carbohydrate moieties of membrane glycoproteins and glycolipids – Unique in everyone but identical twins • Functions – – – – Protection Immunity to infection Defense against cancer Transplant compatibility – Cell adhesion – Fertilization – Embryonic development 3-33 Microvilli • Extensions of membrane (1–2 mm) – Serves to increase cell’s surface area – Best developed in cells specialized in absorption – Gives 15 to 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 3-34 Microvilli Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycocalyx Microvillus Actin microfilaments (a) Figure 3.10a 1.0 m (b) a: © Ed Reschke; b: Biophoto Associates/Photo Researchers, Inc. 0.1 m Figure 3.10b • Actin microfilaments are centered in each microvilli 3-35 Cilia • Hairlike processes 7–10 mm 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 McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mucus Saline layer Epithelial cells 1 2 3 Power stroke (a) Figure 3.12a (b) 4 5 6 7 Recovery stroke Figure 3.12b 3-36 Cilia Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cilia (a) 10 µm a: Custom Medical Stock Photo, Inc. Figure 3.11a 3-37 Cilia Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Axoneme—core of cilia that is the structural basis for ciliary movement • Has 9 + 2 structure of microtubules Axoneme: Peripheral microtubules Central microtubules Dynein arms Shaft of cilium Basal body – Nine pairs form basal body inside the cell membrane • Anchors cilium – Dynein arms ―crawl‖ up adjacent microtubule, bending the cilia • Uses energy from ATP Plasma membrane (b) Dynein arm Central microtubule Axoneme Figure 3.11b,d Peripheral microtubules (d) Cilia • Saline layer – Chloride pumps pump Cl- into ECF – Na+ and H2O follows – Cilia beat freely in saline layer Microvilli Dynein arm Central microtubule Peripheral microtubules (c) 0.15 m c: © Biophoto Associates/Photo Researchers, Inc. Figure 3.11c 3-38 Cystic Fibrosis • Saline layer at cell surface due to chloride pumps move Cl- out of cell. Na+ ions and H2O follow Copyright © The McGraw-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 3.12a • Thick mucus plugs pancreatic ducts and respiratory tract – Inadequate digestion of nutrients and absorption of oxygen – Chronic respiratory infections – Life expectancy of 30 3-39 Flagella • Tail of a sperm—only functional flagellum • Whiplike structure with axoneme identical to cilium – Much longer than cilium – Stiffened by coarse fibers that support the tail • Movement is more undulating, snakelike – No power stroke or recovery stroke as in cilia 3-40 Membrane Transport • Expected Learning Outcomes – Explain what is meant by a selectively permeable membrane. – Describe the various mechanisms for transporting material through the plasma membrane. – Define osmolarity and tonicity and explain their importance. 3-41 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 require 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 other 3-42 Filtration • Filtration—process in which particles are driven through a selectively permeable Solute membrane by hydrostatic Water pressure (force exerted Capillary wall on a membrane by water) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood pressure in capillary forces water and small solutes such as salts through narrow clefts between capillary cells. Red blood cell • Examples – Filtration of nutrients through gaps in blood capillary walls into tissue fluids – Filtration of wastes from the blood in the kidneys while holding back blood cells and proteins Clefts hold back larger particles such as red blood cells. Figure 3.13 3-43 Simple Diffusion • Simple diffusion—the net movement of particles from area of high concentration to area of low concentration – 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 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Figure 3.14 3-44 Simple Diffusion • 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 3-45 Simple Diffusion • 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 3-46 Osmosis • Osmosis—flow of water from one side of a selectively permeable membrane to the other Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Side A Side B – From side with higher water Solute concentration to side with Water lower water concentration – Reversible attraction of water to solute particles forms (a) Start hydration spheres – Makes those water molecules less available to diffuse back to the side from which they came 3-47 Osmosis • Aquaporins—channel proteins in plasma membrane specialized for passage of water – 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 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Side A Side B Solute Water (a) Start Figure 3.15a 3-48 Osmosis • Osmotic pressure— amount of hydrostatic pressure required to stop osmosis • Reverse osmosis— pressure applied to one side, overrides pressure, drives against concentration gradient – Heart drives water out of capillaries by reverse osmosis—capillary filtration Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Osmotic pressure Hydrostatic pressure (b) 30 minutes later Figure 3.15b 3-49 Osmolarity and Tonicity • One osmole = 1 mole of dissolved particles – 1 M NaCl (1 mole Na+ ions + 1 mole Cl- ions) thus 1 M NaCl = 2 osm/L • Osmolarity—number of osmoles of solute per liter of solution 3-50 Osmolarity and Tonicity • Osmolality—number of osmoles of solute per kilogram of water • Physiological solutions are expressed in milliosmoles per liter (mOsm/L) – Blood plasma = 300 mOsm/L – Osmolality similar to osmolarity at concentration of body fluids: less than 1% difference • Tonicity—ability of a solution to affect fluid volume and pressure in a cell – Depends on concentration and permeability of solute 3-51 Osmolarity and Tonicity • 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 3-52 Effects of Tonicity on RBCs Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (a) Hypotonic (b) Isotonic (c) Hypertonic © Dr. David M. Phillips/Visuals Unlimited Figure 3.16a Figure 3.16b Figure 3.16c Hypotonic, isotonic, and hypertonic solutions affect the fluid volume of a red blood cell. Notice the crenated and swollen cells. 3-53 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 releases them, unchanged, on the other • Saturation – As the solute concentration rises, the rate of transport rises, but only to a point—transport maximum (Tm) • Two types of carrier-mediated transport – Facilitated diffusion and active transport 3-54 Carrier-Mediated Transport Rate of solute transport (molecules/sec passing through plasma membrane) Copyright © The McGraw-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 3-55 Carrier-Mediated Transport • Uniport – Carries only one solute at a time • Symport – Carries two or more solutes simultaneously in same direction (cotransport) • Antiport – Carries two 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 3-56 Carrier-Mediated Transport • 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 McGraw-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. 3-57 Carrier-Mediated 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 Ca2+ out of cell 3-58 Carrier-Mediated Transport Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Each pump cycle consumes one ATP and exchanges three Na+ for two K+ Glucose Na+ Apical surface SGLT • Keeps the K+ concentration higher and the Na+ concentration lower within the cell than in ECF • Necessary because Na+ and K+ constantly leak through membrane – Half of daily calories utilized for Na+−K+ pump Cytoplasm Na+– K+ pump ATP ADP + Pi Basal surface Na+ 3-59 Carrier-Mediated Transport • 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 • Regulation of cell volume – ―Fixed anions‖ attract cations causing osmosis – Cell swelling stimulates the Na+−K+ pump to ion concentration, osmolarity and cell swelling 3-60 Carrier-Mediated Transport • Maintenance of a membrane potential in all cells – Pump keeps inside more negative, outside more positive – Necessary for nerve and muscle function • Heat production – Thyroid hormone increases number of Na+−K+ pumps – Consume ATP and produce heat as a by-product 3-61 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 • 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 3-62 Vesicular Transport Copyright © The McGraw-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 3-63 Phagocytosis keeps tissues free of debris and infectious microorganisms Vesicular Transport • 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 3-64 Vesicular Transport Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Extracellular molecules Receptor Coated pit Clathrincoated vesicle Clathrin 1 Extracellular molecules bind to receptors on plasma membrane; receptors cluster together. 2 Plasma membrane sinks inward, forms clathrin-coated pit. (all): Company of Biologists, Ltd. 3 Pit separates from plasma membrane, forms clathrin-coated vesicle containing concentrated molecules from ECF. Figure 3.22 Receptor-mediated endocytosis 3-65 Vesicular Transport • 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 3-66 Vesicular Transport Copyright © The McGraw-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 © Don Fawcett/Photo Researchers, Inc. 0.25 m • Transport of material across the cell by capturing it on one side and releasing it on the other • Receptor-mediated endocytosis moves it into the cell and exocytosis moves it out the other side – Insulin 3-67 Vesicular Transport • Exocytosis – Secreting material – Replacement of plasma membrane removed by endocytosis Copyright © The McGraw-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 3.24a,b 3-68 The Cell Interior • Expected Learning Outcomes – List the main organelles of a cell, describe their structure, and explain their functions. – Describe the cytoskeleton and its functions. – Give some examples of cell inclusions and explain how inclusions differ from organelles. 3-69 The Cell Interior • Structures in the cytoplasm – Organelles, cytoskeleton, and inclusions – All embedded in a clear gelatinous cytosol 3-70 The 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 the cell as a whole • Composed of: – Microfilaments: 6 nm thick, actin, forms terminal web – Intermediate fibers: 8–10 nm, support, strength, and structure – Microtubules: 25 nm, tubulin, movement 3-71 Cytoskeleton Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Microvilli Microfilaments Terminal web Secretory vesicle in transport Desmosome Lysosome Kinesin Microtubule Intermediate filaments Intermediate filaments Microtubule in the process of assembly Centrosome Microtubule undergoing disassembly Nucleus Mitochondrion (a) Basement membrane Hemidesmosome Figure 3.25a 3-72 EM and Fluorescent Antibodies Demonstrate Cytoskeleton Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (b) 15 m © K.G. Murti/Visuals Unlimited Figure 3.25b 3-73 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 McGraw-Hill Companies, Inc. Permission required for reproduction or display. (a) (b) (c) Microtubule Protofilaments Dynein arms Tubulin Figure 3.26 3-74 Organelles • Internal structures, carry out specialized metabolic tasks • Membranous organelles – Nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, and Golgi complex • Nonmembranous organelles – Ribosomes, centrosomes, centrioles, basal bodies 3-75 The Nucleus • Nucleus—largest organelle (5 mm 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 3-76 The Nucleus Cont. – 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 (threadlike matter) composed of DNA and protein – Nucleoli—one or more dark masses where ribosomes are produced 3-77 The Nucleus Copyright © The McGraw-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 3.27a Figure 3.27b 3-78 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 3-79 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 3-80 Smooth and Rough ER Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Rough endoplasmic reticulum Ribosomes Cisternae (c) Smooth endoplasmic reticulum Figure 3.28c 3-81 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 3-82 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 3-83 Golgi Complex Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Golgi vesicles Golgi complex Figure 3.29 600 nm Visuals Unlimited 3-84 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 3-85 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 (H2O2) – Catalase breaks down excess peroxide to H2O and O2 – Neutralize free radicals, detoxify alcohol, other drugs, and a variety of blood-borne toxins – Break down fatty acids into acetyl groups for mitochondrial use in ATP synthesis • In all cells, but abundant in liver and kidney 3-86 Lysosome and Peroxisomes Copyright © The McGraw-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 3.30a Figure 3.30b 3-87 Mitochondria • Mitochondria—organelles specialized for synthesizing ATP • Variety of shapes: spheroid, rod-shaped, kidney-shaped, or threadlike • Surrounded by a double unit membrane Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. – Inner membrane has folds called cristae – Spaces between cristae called matrix • Matrix contains ribosomes, enzymes used for ATP synthesis, small circular DNA molecule – Mitochondrial DNA (mtDNA) Matrix Outer membrane Inner membrane Mitochondrial ribosome Intermembrane space Crista • ―Powerhouses‖ of the cell – Energy is extracted from organic molecules and transferred to ATP Figure 3.31 3-88 Mitochondrion Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Matrix Outer membrane Inner membrane Mitochondrial ribosome Figure 3.31 Intermembrane space Crista 1 m 3-89 (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 suggest that the original bacterium provided the inner membrane, and the host cell’s phagosome provided the outer membrane – Mitochondrial ribosomes are more like bacterial ribosomes 3-90 Evolution of Mitochondrion – Has its own mtDNA • 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 3-91 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 called the centrosome – Play role in cell division 3-92 Centrioles • 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 • Migrate to plasma membrane – Two microtubules of each triplet elongate to form the nine pairs of peripheral microtubules of the axoneme – Cilium reaches full length in less than an hour 3-93 Centrioles Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Figure 3.32a,b Microtubules Protein link Longitudinal view Cross section 0.1 m (a) Cross section (TEM) Microtubules (b) Pair of centrioles 3-94 a: From: Manley McGill, 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 Inclusions • Two kinds of inclusions – Stored cellular products • Glycogen granules, pigments, and fat droplets – Foreign bodies • Viruses, intracellular bacteria, dust particles, and other debris phagocytized by a cell • Never enclosed in a unit membrane • Not essential for cell survival 3-95 Inclusions 3-96