Chapter 2: The Cell. Ryan R. Williams, M.D., Ph.D. August 29 th, 2018 West Los Angeles College

Chapter 2: The Cell Ryan R. Williams, M.D., Ph.D. August 29 th, 2018 West Los Angeles College

Introduction There are two types of cells in the body: Sex cells Sperm in males and oocytes in females Somatic cells All the other cells in the body that are not sex cells 2/75

Cellular Anatomy The cell consists of: Cytoplasm Cytosol Organelles Nonmembranous organelles Membranous organelles Plasmalemma Cell membrane 4/75

Cellular Anatomy Organelles of the Cell Nonmembranous organelles Cytoskeleton Microvilli Centrioles Cilia Flagella Ribosomes 5/75

Figure 2.1 Anatomy of a Typical Cell Microvilli Secretory vesicles Cytosol Lysosome Centrosome Centriole Chromatin Nucleoplasm Nucleolus Nuclear envelope surrounding nucleus Cytoskeleton Plasmalemma Golgi apparatus Mitochondrion Peroxisome Nuclear pores Smooth endoplasmic reticulum Rough endoplasmic reticulum Fixed ribosomes Free ribosomes

Cellular Anatomy Organelles of the Cell Membranous organelles Mitochondria Nucleus Endoplasmic reticulum Golgi apparatus Lysosomes Peroxisomes 7/75

Body Fluids Intracellular fluid (ICF) (inside body cells) Tissue cell Blood cell Blood vessel Interstitial fluid (between body cells) Blood plasma Extracellular fluid (ECF) (outside body cells) Copyright 2017 John Wiley & Sons, Inc. All rights reserved.

The Central Dogma of Biology DNA encodes for RNA RNA encodes for Protein DNA >>> RNA >>> Protein 10/75

Cellular Anatomy Plasmalemma A cell membrane composed of: Phospholipids Glycolipids Protein Cholesterol 11/75

Cellular Anatomy Functions of the Plasmalemma Cell membrane (also called phospholipid bilayer) Major functions: Physical isolation Sense the environment Regulation of exchange with the environment (permeability) Cell-to-cell communication/adhesion/structural support 12/75

Cellular Anatomy Structure of the Plasmalemma Called a phospholipid bilayer Composed of two layers of phospholipid Hydrophillic heads are at the surfaces (inside lining and outside lining) Hydrophobic fatty acids (tails) face toward each other Glycolipids and glycoproteins protrude out and form a glycocalyx coating, mostly one the outside 13/75

Figure 2.3 The Plasmalemma Hydrophillic=loves water Hydrophobic=afraid of water Hydrophilic heads Hydrophobic tails Cholesterol EXTRACELLULAR FLUID Glycolipids of glycocalyx Phospholipid bilayer Integral protein with channel Integral glycoproteins Hydrophobic tails b The phospholipid bilayer Gated channel Cholesterol CYTOPLASM Peripheral proteins = 2 nm Hydrophilic heads Cytoskeleton (Microfilaments) a The plasmalemma

Cellular Anatomy Structure of the Plasmalemma Composed of protein molecules Peripheral proteins: Do not go into membrane Attach to either the intracellular (inside) or extracellular surface (outside) Often attach to the glycerol portions of the fatty acid heads Integral proteins: embedded within the cell membrane Signaling receptors allows for communication between cells Form channels such as gated channels Channels open and close to allow ions (charged atoms) to pass through This creates selective permeability across the membrane (i.e. ions can pass through the membrane only if their specific channel-type is open) The selective permeability allows for an electrical gradient (or charge difference) to form across the membrane 15/75

Figure 2.3 The Plasmalemma Hydrophilic heads Hydrophobic tails Cholesterol EXTRACELLULAR FLUID Glycolipids of glycocalyx Phospholipid bilayer Integral protein with channel Hydrophobic tails Integral glycoproteins b The phospholipid bilayer Gated channel Cholesterol CYTOPLASM Peripheral proteins = 2 nm Hydrophilic heads Cytoskeleton (Microfilaments) a The plasmalemma

Cellular Anatomy Structure of the Plasmalemma Composed of sterol molecules Function to maintain fluidity of the membrane An example is cholesterol 17/75

Figure 2.3 The Plasmalemma Hydrophilic heads Hydrophobic tails Cholesterol EXTRACELLULAR FLUID Glycolipids of glycocalyx Phospholipid bilayer Integral protein with channel Integral glycoproteins Hydrophobic tails b The phospholipid bilayer Cholesterol Gated channel CYTOPLASM Peripheral proteins = 2 nm Hydrophilic heads Cytoskeleton (Microfilaments) a The plasmalemma

Cellular Anatomy Membrane Permeability of the Plasmalemma Permeability=the ability to flow through Passive processes=no energy (i.e. ATP) required Diffusion (includes facilitated) Osmosis Molecules go down-hill Active processes=requires help or energy (ATP) Active transport Endocytosis Exocytosis Molecule go up-hill 19/75

Cellular Anatomy Membrane Permeability of the Plasmalemma Passive process: diffusion Movement of molecules from an area of high concentration to an area of low concentration Permeablity, concentration gradient, molecule size and charge, temperature affect the rate of movement Small inorganic ions and small molecules are involved 20/75

Figure 2.4 Membrane Permeability: Active and Passive Processes (1 of 6) Diffusion is the movement of molecules from an area of higher concentration to an area of lower concentration. The difference between the high and low concentrations is a concentration gradient. In diffusion, molecules move down a concentration gradient until the gradient is eliminated. Diffusion Factors Affecting Rate: Membrane permeability; magnitude of the concentration gradient; size, charge, and lipid solubility of the diffusing molecules; presence of membrane channel proteins; temperature Extracellular fluid Plasmalemma CO 2 Example: When the concentration of CO 2 inside a cell is greater than outside the cell, CO 2 diffuses out of the cell and into the extracellular fluid. Substances Involved (all cells): Gases, small inorganic ions and molecules, and lipid-soluble materials 21/75

Cellular Anatomy Membrane Permeability of the Plasmalemma Passive process: osmosis Movement of water molecules from an area of high concentration of water to an area of low concentration of water Permeability, concentration gradient, and opposing pressure affect the rate of movement Only water molecules are involved 22/75

Cellular Anatomy Membrane Permeability of the Plasmalemma Passive process: facilitated diffusion Solutes are passively transported by a carrier protein Also dependent on concentration gradient, size and charge of the solute, temperature, and number of carrier proteins Glucose and amino acids may be involved 23/75

Figure 2.4 Membrane Permeability: Active and Passive Processes (3 of 6) Facilitated diffusion Glucose Plasmalemma In facilitated diffusion, solutes are passively transported across a plasmalemma by a carrier protein. As in simple diffusion, the direction of movement follows the concentration gradient. Factors Affecting Rate: Magnitude of the concentration gradient; size, charge, and solubility of the solutes; temperature; availability of carrier proteins Substances Involved (all cells): Glucose and amino acids Extracellular fluid Receptor site Carrier protein Cytoplasm Carrier protein releases glucose into cytoplasm Example: Nutrients that are insoluble in lipids or too large to fit through membrane channels may be transported across the plasmalemma by carrier proteins. Many carrier proteins move a specific substance in one direction only, either into or out of the cell, after first binding the substance at a specific receptor site. 24/75

Cellular Anatomy Membrane Permeability of the Plasmalemma Active process: active transport Solutes are actively transported or pumped by acarrier protein regardless of the concentration gradient ATP, number of carrier proteins affect the rate of movement by providing energy Sodium, potassium, calcium, and magnesium ions are involved 25/75

Figure 2.4 Membrane Permeability: Active and Passive Processes (4 of 6) Active transport Using active transport, carrier proteins can move specific substances across the plasmalemma despite an opposing concentration gradient. Carrier proteins that move one solute in one direction and another solute in the opposite direction are called exchange pumps. Factors Affecting Rate: Availability of carrier proteins, solutes, and ATP Substances Involved: Na +, K +, Ca 2+, Mg 2+ (all cells); other solutes in special cases Sodium potassium exchange pump Cytoplasm Extracellular fluid 2 K + ATP ADP Example: The most common example of active transport is the sodium potassium exchange pump. For each molecule of ATP consumed, three sodium ions are ejected from the cell and two potassium ions are reclaimed from the extracellular fluid. 3 Na + 26/75

Cellular Anatomy Membrane Permeability of the Plasmalemma Active process: endocytosis Pinocytosis: vesicles bring small molecules into the cell A variety of stimuli affect the rate of movement (not fully understood) Extracellular fluid is involved Phagocytosis: vesicles bring larger solid particles into the cell Presence of extracellular pathogens affects the rate of movement Bacteria, viruses, foreign matter, and cell debris are involved Receptor mediated endocytosis Target molecules (ligands) bind to specific receptor proteins on the membrane surface, triggering vesicle formation 27/75

Figure 2.4 Membrane Permeability: Active and Passive Processes (5 of 6) Endocytosis Endocytosis is the packaging of extracellular materials into a vesicle (a membrane-bound sac) for importation into the cell. Pinocytosis Phagocytosis Receptor-mediated endocytosis In pinocytosis, vesicles form at the plasmalemma and bring extracellular fluid and small molecules into the cell. This process is often called cell drinking. In phagocytosis, vesicles form at the plasmalemma to bring solid particles into the cell. This process is often called cell eating. Extracellular fluid Target molecules Cell Pinocytotic vesicle forming Factors Affecting Rate: Stimulus and mechanism not understood Substances Involved: Extracellular fluid and its associated solutes Example: Water and small molecules within a vesicle may enter the cytoplasm through carriermediated transport or diffusion. Factors Affecting Rate: Presence and abundance of extracellular pathogens or debris Substances Involved: Bacteria, viruses, cell debris, and other foreign material Pseudopodium extends to surround object Cell Phagocytic vesicle Example: Large particles are brought into the cell when cytoplasmic extensions (called pseudopodia) engulf the particle and form a phagocytic vesicle. Receptor proteins Cytoplasm Vesicle containing target molecules In receptor-mediated endocytosis, target molecules bind to specific receptor proteins on the membrane surface, triggering vesicle formation. Factors Affecting Rate: Number of receptors on the plasmalemma and the concentration of target molecules (called ligands) Substances Involved (all cells): Many examples, including cholesterol and iron ions Example: Each cell has specific sensitivities to extracellular materials, depending on the kind of receptor proteins present in the plasmalemma.

Cellular Anatomy Membrane Permeability of the Plasmalemma Active process: exocytosis The release of intracellular material to the extracellular area Requires ATP and calcium ions for movement Fluid and cellular waste and secretory products are involved 31/75

Cellular Anatomy Extensions of the Plasmalemma: Microvilli Fingerlike projections of the plasmalemma Absorb material and nutrients from the extracellular fluid (ECF) Increase the surface area of the plasmalemma Microvilli can bend back and forth in a waving manner This movement helps to circulate extracellular fluid This movement helps absorb nutrients 32/75

Cellular Anatomy The Cytoplasm Term for all of the intracellular material Cytosol Consists of the ICF (intracellular fluid) Consists of nutrients, protein, and waste products Organelles These are intracellular structures that perform specific functions 34/75

Cellular Anatomy The Cytoplasm Cytosol Contains a higher concentration of potassium ions and a lower concentration of sodium ions, compared to the ECF Consists of a net negative charge Contains a high concentration of protein Proteins have a net negatively charge at physiologic ph Contains a small quantity of carbohydrates Contains a large reserve of amino acids and lipids K + Na + K + Na + Protein - 35/75

Cellular Anatomy Nonmembranous Organelles The cytoskeleton consists of: Microfilaments Intermediate filaments Thick filaments Microtubules 36/75

Cellular Anatomy Nonmembranous Organelles Microfilaments: consist mostly of actin protein Anchor proteins to cytoskeleton or membrane Anchor plasmalemma to the cytoplasm Produce movement of the cell or a change in the cell s shape 37/75

Cellular Anatomy Nonmembranous Organelles Intermediate filaments Provide strength Stabilize the position of organelles Transport material within the cytosol Thick filaments: composed of myosin protein Found in muscle cells: involved in muscle contraction 38/75

Cellular Anatomy Nonmembranous Organelles Microtubules: composed of tubulin protein Involved in the formation of centrioles perform a function during cell reproduction Involved in moving duplicated chromosomes to opposite poles of the cell perform a function during cell reproduction Involved in anchoring and moving organelles Involved in moving the entire cell Involved in moving material across the surface of the cell 39/75

Figure 2.5 The Cytoskeleton Microvilli Microfilaments Plasmalemma SEM 30,000 Terminal web b A SEM image of the microfilaments and microvilli of an intestinal cell. Mitochondrion Intermediate filaments a The cytoskeleton provides strength and structural support for the cell and its organelles. Interactions between cytoskeletal elements are also important in moving organelles and in changing the shape of the cell. Endoplasmic reticulum Microtubule Secretory vesicle c LM 3200 Microtubules in a living cell, as seen after fluorescent labeling.

Cellular Anatomy Nonmembranous Organelles Examples of structures that microtubules form Centrioles Cilia Flagella Note the difference Microfilaments (i.e. actin) form microvilli (for absorption Microtubules form cilia (for movement) Both are protrusions of the cell membrane, but cilia are larger 41/75

Table 2.2 A Comparison of Centrioles, Cilia, and Flagella

Figure 2.6 Centrioles and Cilia a A centriole consists of nine microtubule triplets (9 + 0 array). The centrosome contains a pair of centrioles oriented at right angles to one another. Microtubules Plasmalemma Microtubules Basal body b A cilium contains nine pairs of microtubules surrounding a central pair (9 + 2 array). Power stroke Return stroke TEM 240,000 c A single cilium swings forward and then returns to its original position. During the power stroke, the cilium is relatively stiff, but during the return stroke, it bends and moves parallel to the cell surface.

Cellular Anatomy Nonmembranous Organelles Ribosomes Free ribosomes: float in the cytoplasm Fixed ribosomes: attached to the endoplasmic reticulum Both are involved in producing protein 44/75

Cellular Anatomy Membranous Organelles Double-membraned organelles Mitochondria: produce ATP Nucleus: contains chromosomes (DNA) Endoplasmic reticulum: network of hollow tubes Golgi apparatus: modifies protein Lysosomes: contain cellular digestive enzymes Peroxisomes: contain catalase to break down hydrogen peroxide 46/75

Figure 2.8 Mitochondria Inner membrane Cytoplasm of cell Cristae Matrix Organic molecules and O 2 CO 2 ATP Outer membrane Matrix Cristae Enzymes TEM 61,776

Cellular Anatomy Membranous Organelles Nucleus: control center of the cell Nucleoplasm Nuclear envelope Perinuclear space Nuclear pores Nuclear matrix 48/75

Figure 2.9ab The Nucleus Perinuclear space Nucleoplasm Chromatin Nucleolus Nuclear envelope Nuclear pores TEM 4828 a TEM showing important nuclear structures. Nuclear envelope Perinuclear space Nuclear pore b A nuclear pore and the perinuclear space. Chromatin = Loosely coiled DNA and associated proteins in a non-dividing cell Chromosome = Super-coiled DNA in a dividing cell Nuclear envelope is a double lipid bilayer (double membrane)

Figure 2.10 Chromosome Structure Histones Nucleosome Nucleus of nondividing cell a Chromatin in nucleus In cells that are not dividing, the DNA is loosely coiled, forming a tangled network known as chromatin. Sister chromatids Loosely coiled nucleosomes, forming chromatin. DNA double helix Centromere Kinetochore Supercoiled region b Dividing cell Visible chromosome When the coiling becomes tighter, as it does in preparation for cell division, the DNA becomes visible as distinct structures called chromosomes. Chromosomes are composed of two sister chromatids which attach at a single point, the centromere. Kinetochores are the region of the centromere where spindle fibers attach during mitosis.

Cellular Anatomy Membranous Organelles Endoplasmic reticulum (ER) There are two types Rough endoplasmic reticulum (RER) Consists of fixed ribosomes Synthesizes proteins Smooth endoplasmic reticulum (SER) Synthesizes lipids, steroids, and carbohydrates Storage of calcium ions Detoxification of toxins 51/75

Figure 2.11 The Endoplasmic Reticulum Ribosomes Rough endoplasmic reticulum with fixed (attached) ribosomes Free ribosomes Smooth endoplasmic reticulum Endoplasmic Reticulum TEM 11,000 Cisternae

Cellular Anatomy Membranous Organelles Golgi apparatus Synthesis and packaging of secretions Packaging of enzymes (modifies protein) Renewal and modification of the plasmalemma The FedEx of the cell 53/75

Cellular Anatomy Membranous Organelles Lysosomes Fuse with phagosomes to digest materials Recycle damaged organelles Sometimes rupture, thus killing the entire cell (called autolysis) 54/75

Cellular Anatomy Membranous Organelles Peroxisomes Contains catalase converts hydrogen peroxide to water and oxidants oxidants steal electrons make free radicals Required for the catabolism of lipids Abundant in liver cells Note the ending ase means enzyme -Lipase -Protease Enzymes function to modify or change the structure of proteins, lipids, and carbohydrates 55/75

Cellular Anatomy Membrane Flow This is the continuous movement and recycling of the cell membrane Transport vesicles connect the endoplasmic reticulum with the Golgi apparatus Secretory vesicles connect the Golgi apparatus with the plasmalemma Vesicles remove and recycle segments of the plasmalemma 56/75

Figure 2.13 Functions of the Golgi Apparatus (1 of 3) Cisterna Forming (cis) face Cytoplasm Golgi Apparatus Synthesis and Packaging of Secretions: Steps Transport vesicle 2 Secretory products are packaged into transport vesicles that eventually bud off from the ER. These transport vesicles then fuse to create the forming (cis) face of the Golgi apparatus. Rough ER Endoplasmic Reticulum mrna Ribosome 1 Protein and glycoprotein synthesis occurs in the rough endoplasmic reticulum (RER). Some of these proteins and glycoproteins remain within the ER.

Figure 2.13 Functions of the Golgi Apparatus (2 of 3) Plasmalemma Secretory material Packaging of Enzymes for Use in the Cytosol Renewal or Modification of the Plasmalemma Synthesis and Packaging of Secretions Plasmalemma Exocytosis at the surface of a cell Cytoplasm Secretory vesicle TEM 75,000 Lysosome Maturing (trans) face Secretory vesicle Synthesis and Packaging of Secretions: Steps 4 The maturing (trans) face generates vesicles that carry materials away from the Golgi apparatus. Cisterna Forming (cis) face 3 Each cisterna physically moves from the forming face to the maturing face, carrying with it its associated proteins. This process is called cisternal progression. Cytoplasm Golgi Apparatus

Intercellular Attachment Many cells form permanent or temporary attachment to other cells Attach via cell adhesion molecules (CAMs) Attach via cellular cement (proteoglycans) Examples of Intercellular Attachment Communicating junctions Adhering junctions Tight junctions Anchoring junctions Note: Intra- means inside (i.e. intracellular vs extracellular) Inter- means between (i.e. between two cells) 59/75

Intercellular Attachment Communicating Junctions (aka gap junctions) Hold cells together via proteins called connexons This protein is a type of channel protein 60/75

Figure 2.14ab Cell Attachments Tight junction Embedded proteins (connexons) Zonula adherens Terminal web Button desmosome b Communicating junctions permit the free diffusion of ions and small molecules between two cells. Hemidesmosome a A diagrammatic view of an epithelial cell showing the major types of intercellular connections. Communicating junction (gap junction)

Intercellular Attachment Adhering and anchoring Junctions Tight junctions aka occluding junctions Prevent the movement of water and other molecules from passing between the cells Adhesion belt (zona adherens) sheetlike cell to cell Desmosome (macula adherens) small, localized cell to cell Hemidesmosomes cell to ECM (extracellular matrix) usually at base of cell (i.e. connects cells to basal lamina) 62/75

Figure 2.14ac Cell Attachments Tight junction Interlocking junctional proteins Tight junction Zonula adherens Terminal web Hemidesmosome Button desmosome a A diagrammatic view of an epithelial cell showing the major types of intercellular connections. Communicating junction c Zonula adherens A tight junction is formed by the fusion of the outer layers of two plasmalemmae. Tight junctions prevent the diffusion of fluids and solutes between the cells. 63/75

Figure 2.14ae Cell Attachments Tight junction Hemidesmosome Zonula adherens Terminal web Button desmosome Communicating junction a A diagrammatic view of an epithelial cell showing the major types of intercellular connections. Clear layer Dense layer Basal lamina e Hemidesmosomes attach an epithelial cell to extracellular structures, such as the protein fibers in the basal lamina. 64/75

The Cell Life Cycle Cell reproduction consists of special events Interphase Mitosis Prophase Metaphase Anaphase Telophase Cytokinesis Overlaps with anaphase and telophase 65/75

The Cell Life Cycle Interphase Everything inside the cell is duplicating Consists of G 1, S, and G 2 phases G 1 : duplication of organelles and protein synthesis S: Chromosome replication and DNA synthesis and histone synthesis G 2 : protein synthesis G o is before G 1 and indicated the cell is not duplicating, i.e. the cell is performing its regular functions and is in a resting state 66/75

The Cell Life Cycle Cell Reproduction (Mitosis) ~PMAT Prophase Chromosomes condense and form sister chromatids Microtubules bind chromatids Metaphase Paired chromatids line up in the middle of the nuclear region Anaphase Paired chromatids separate to opposite poles of the cell Telophase Two new nuclear membranes begin to form 67/75

Figure 2.17 Mitosis (1 of 2) Interphase Prophase Metaphase Early prophase Nuclear membrane Late prophase Centromere Chromosomal microtubules Nucleus Spindle fibers Astral rays Chromosome with two sister chromatids Metaphase plate Centrioles (two pairs) Chromosomal microtubules

Figure 2.17 Mitosis (2 of 2) Anaphase Telophase Cytokinesis Daughter cells Daughter chromosomes Cleavage furrow

The Cell Life Cycle Cytokinesis Cell membrane begins to invaginate and divide, thus forming two new cells Many times this phase actually begins during anaphase This is the conclusion of cell reproduction 70/75

Figure 2.15 The Cell Life Cycle INTERPHASE G 1 Normal cell functions plus cell growth, duplication of organelles, protein synthesis S DNA replication, synthesis of histones G 2 Protein synthesis THE CELL CYCLE M Indefinite period G 0 Specialized cell functions MITOSIS AND CYTOKINESIS (See Figure 2.17)

Animations to Review Module 2.2 The Plasma Membrane Membrane Functions Transport Across the Plasma Membrane Module 2.3 The Cytoplasm Protein synthesis Module 2.5 Cell Division Gametogenesis 72/75