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Introduction to Cellular Structure • All organisms are composed of cells – Single-cell organisms humans • Cells are responsible for all structural and functional properties of a living organism Development of Cell Theory • Cytology—scientific study of cells – Began in 1665 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 • Modern cell theory: – All organisms are 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. Cells • The cell is the structural and functional unit of life • Human adults are made up of ~100 trillion cells • Each cell has an outer boundary called the plasma (cell) membrane which isolates the fluid within the cell from the fluid that surrounds the cell • Some cells function individually, while most cells work together with similar cells forming tissues • Within each cell is a collection of subcellular components called organelles which accomplish a specific task for the cell – membranous – nonmembranous (inclusions) Cell Shapes • 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 Cell Shapes and Sizes Squamous Cuboidal Columnar Polygonal Stellate Spheroid Discoid Fusiform (spindle-shaped) Fibrous Cell Sizes • Human cell size – approx: 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 – The surface area of a cell is proportional to the square of its diameter. The volume of a cell is proportional to the cube of its diameter • Nutrient absorption and waste removal utilize surface area – Overgrown cells may rupture Cells grow mostly in volume: 20 m Growth 20 m 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) 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) Plasma membrane Nucleus Nuclear envelope Mitochondria Golgi vesicle Golgi complex Ribosomes 2.0 m 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 • Cytoplasm – Organelles – Cytoskeleton (microtubules) – Cytosol (intracellular fluid, ICF) • Extracellular fluid (ECF) – Fluid outside of cell The Plasma Membrane - Appears as a pair of dark parallel lines around cell (viewed with the electron microscope) • Plasma membrane—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 Plasma membrane of upper cell Intercellular space Plasma membrane of lower cell Nuclear envelope Nucleus (a) 100 nm © Don Fawcett/Photo Researchers, Inc. Cellular Membranes • The outer boundary of the cell as well as the boundary of many of the internal organelles is made of a cellular membrane 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 • Composed primarily of phospholipids that are arranged in a bilayer (2 layers) with proteins, carbohydrates and cholesterol molecules are integrated within 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 Phospholipid Models Cellular Membrane Anatomy • 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 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 (ICF) and extracellular fluid (composed of polar amino acids) – Have hydrophobic regions that pass back and forth through the lipid of the membrane (composed of nonpolar amino acids) • Peripheral membrane protein – associated only with the intracellular surface of the cell membrane (located in the ICF) – capable of detaching and moving into the cytosol to interact with other molecules within the cell Integral Membrane Protein Structure Integral Membrane Protein Functions Membrane Carbohydrates • The small polysaccharides that are part of the plasma membrane are always immersed in the ECF – covalently bound to an integral membrane protein or a phospholipid head • 2 varieties – Glycolipids • polysaccharides are covalently bound to the polar head of a phospholipid – Glycoproteins • polysaccharides are covalently bound the extracellular portion of an integral membrane protein 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 3-21 Second-Messenger Systems • 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), activating a signaling cascade. • cAMP activates a kinase in the cytosol 1 A messenger such as epinephrine (red triangle) binds to a receptor in the plasma membrane. First messenger Receptor G Adenylate cyclase • Kinases add phosphate groups to other cellular enzymes 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 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 – 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! 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 Carriers or Pumps • Transmembrane proteins bind to glucose, electrolytes, and other solutes – Transfer them across membrane • Pumps consume ATP in the process 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. 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 extracellular material – Special events: sperm–egg binding; binding of immune cell to a cancer cell requires CAMs Microvilli Glycocalyx Microvillus Actin microfilaments (a 1. 0 m 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” 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 Composed of microtubules • 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 Mucus Saline layer Epithelial cells 1 2 3 Power stroke (a) (b) 4 5 6 7 Recovery stroke Cilia Cilia (a) 10 µm Cilia • Axoneme—core of cilia that is the structural basis for ciliary movement • Composed of : microtubules (anchor the cilia) and Dynein (a protein which uses ATP to bend the microtubule). Shaft of cilium • Saline layer – Chloride pumps pump Cl- into ECF – Na+ and H2O follows – Cilia beat freely in saline layer Flagella • Tail of a sperm—only functional flagellum • Whiplike structure with axoneme identical to the cilia – Much longer than cilium – Stiffened by coarse fibers that support the tail • Movement is more undulating, snakelike Cystic Fibrosis • Saline layer at cell surface due to chloride pumps move Cl- out of cell. Na+ ions and H2O follow Mucus • Cystic fibrosis—hereditary disease in which cells make chloride pumps, but fail to install them in the plasma membrane – Chloride pumps fail to create adequate saline layer on cell surface • Thick mucus plugs pancreatic ducts and respiratory tract – Inadequate digestion of nutrients and absorption of oxygen – Chronic respiratory infections – Life expectancy of 30 Saline layer Epithelial cells (a) The Cytoskeleton • Cytoskeleton—collection of filaments and cylinders – Cell scaffolding • Composed of: – Microfilaments: 6 nm thick, actin, forms terminal web – Intermediate fibers: 8–10 nm, support, strength, and structure – Microtubules: 25 nm, tubulin, movement 3-32 Cytoskeleton Microvilli Microfilaments Secretory vesicle in transport Desmosome Terminal web Lysosome Kinesin Microtubule Intermediate filaments Centrosome Microtubule undergoing disassembly Intermediate filaments Microtubule in the process of assembly Nucleus Mitochondrion (a) (b) Basement membrane Hemidesmosome 15 m 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 The Nucleus • Largest organelle of a cell – only intracellular organelle visible with a compound light microscope (plasma membrane is also visible) • Consists of 3 parts: – nuclear envelope – Chromatin (threadlike matter composed of DNA and protein) – nucleolus (ribosome production) • Some cells are anuclear (no nuclei) and some are multinucleated Nuclear Structure Nuclear pores Nucleolus Nucleoplasm Nuclear envelope (a) Interior of nucleus 2 mm (b) Surface of nucleus 1.5 mm ER • Interconnected maze of membranous tubes and sacs • Smooth ER – Storage site of intracellular calcium (Ca2+) – Location of enzymes which: • synthesize lipids – steroids – phospholipids • hydrolyze drugs and toxins • Rough ER – ribosomes on the outer surface of the ER synthesize proteins that are then moved to the Golgi complex for modification Endoplasmic Reticulum (ER) Ribosomes • Site of protein synthesis in a cell • Move around the cell between 2 locations – floating in the ICF, ribosomes are “free” • synthesize proteins that remain within the cell – temporarily attached to the membrane of the endoplasmic reticulum, ribosomes are “membrane-bound” • synthesize: – integral membrane proteins – secreted proteins which are exported out of the cell into the ECF to go elsewhere in the body • once the ribosome finishes making the protein, it detaches from the ER becoming “free” again Golgi Complex • Layers of flattened membranous sacs • Modifies proteins synthesized at the rough ER – addition of carbohydrates to make glycoproteins – the removal of some amino acids • makes these proteins biologically active • packages the protein into membrane-bound Golgi vesicles Golgi Complex Golgi vesicles Golgi complex 600 nm Centrioles • a short cylindrical assembly of microtubules. Microtubules Protein link Cross section 0.1 m (a) Cross section (TEM) Microtubules (b) Pair of centrioles – Play role in cell division Longitudinal view Lysosomes • Spherical membranous bags containing hydrolytic (digestive) enzymes – hydrolyze bacteria and viruses that infect a cell – hydrolyze old, worn out organelles • allows cells to “recycle” the macromolecules that make up organelles Lysosomes 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 Mitochondria • Mitochondria—organelles specialized for synthesizing ATP • Variety of shapes: spheroid, rod-shaped, kidney-shaped, or threadlike • Surrounded by a double membrane – Inner membrane has folds called cristae (increase surface area) – Spaces between cristae called matrix • Matrix contains ribosomes, enzymes used for ATP synthesis, small circular DNA molecule – Mitochondrial DNA (mtDNA) • “Powerhouses” of the cell – Energy is extracted from organic molecules and transferred to ATP Matrix Outer membrane Inner membrane Mitochondrial ribosome Intermembrane space Crista Evolution of the 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 – 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