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Chapter 3: The Cellular Level Of Organization BIO 137 ANATOMY & PHYSIOLOGY I The Cell • Adult humans contain about 70 trillion cells (260 different types) • Differentiation - Process where a cell becomes specialized • The cell is the smallest unit of life that can survive on its own • Highly organized for metabolism • Exhibits the characteristics of life • All cells have the same DNA, but different genes are expressed in different cell types Cell Size ands Shape • Cells vary considerably in size and shape – 7.5µm - 500µm A Generalized Cell • All eukaryotic cells are composed of three main parts: 1. Plasma membrane or “plasmalemma” 2. Cytoplasm - a gelatin-like substance, plus structural fibers and organelles (but not the nucleus) 3. Nucleus - contains the genetic material of the cell A Eukaryotic Cell Eukaryotic vs Prokaryotic Cells • Eukaryotic Cells • Prokaryotic Cells – Plasma membrane and/or cell wall surrounds the cell – Have a cell wall surrounding a plasma membrane – Nucleus contains linear DNA – No nucleus – Support comes from the cytoskeleton – Cytoplasm contains organelles – Closed circular DNA located in the cytosol – Have no organelles – Cytosol is present Eukaryotic and Prokaryotic Cells Pili Nucleoid: region where the cell’s DNA is located (not enclosed by a membrane) Ribosomes Plasma membrane Cell wall Capsule (a) A typical rod-shaped bacterium Flagella (b) A thin section through th bacterium Bacillus coag (TEM) Eukaryotic Cells • One of the most distinguishing features of Eukaryotic cells is Compartmentalization. • This is achieved by the endomembrane system and numerous organelles A Generalized Cell The plasma membrane forms the cell’s outer boundary and separates the cell’s internal environment from the outside environment. – It is a selectively permeable barrier, allowing the passage of some things and not others. – It plays a role in cellular communication. The Plasma Membrane • Phospholipid bilayer surrounds a cell, separating it from the external environment • Phospholipid Structure – Hydrophilic head and 2 hydrophobic tails – Hydrophobic tails aggregate together in water, forming a bilayer Permeability of the Lipid Bilayer • Plasma membrane acts as a barrier in a cell – Selectively permeable • Hydrophobic molecules – Are lipid soluble and can pass through the membrane rapidly • Hydrocarbons, CO2, O2 • Polar molecules – Do not cross the membrane rapidly • Ions, polar molecules (sugars, water) Fluid Mosaic Model • The Fluid Mosaic Model describes the arrangement of molecules within the membrane: – A sea of phospholipids with protein “icebergs” floating in it. • Membrane is a fluid structure with a “mosaic” of various proteins embedded in it – Fluidity allows movement The Plasma Membrane Other features of the Plasma Membrane • Integral proteins - extend into or through the bilayer. – Transmembrane proteins (most integral proteins) span the entire lipid bilayer. – Peripheral proteins attach to the inner or outer surface but do not extend through the membrane. • Glycoproteins and glycolipids for cell identification The Plasma Membrane Membrane Proteins • Different cells have different proteins embedded in the membrane • Membrane function is determined by its membrane proteins • Membrane protein functions include: – Transport (Channel proteins) – Enzymatic activity – Communication (Receptor proteins) – Cell-cell recognition (Cell surface markers) – Attachment (peripheral proteins) – Cellular junctions (Cell adhesion molecules) The Plasma Membrane Examples of different membrane proteins include Ion channels Carriers Receptors The Plasma Membrane Examples of different membrane proteins include Enzymes Linkers Cell identity markers Plasma Membrane Permeability • Plasma membrane is selectively permeable • Allows only hydrophobic substances, CO2 and O2 to pass through freely • Other hydrophilic substances must enter a cell through other means – Channel or carrier proteins – Bulk transport Movements in and out of a cell • • • • • • Diffusion Facilitated Diffusion Osmosis Filtration Active transport Bulk transport – Endocytosis – Exocytosis Membrane Traffic: Passive Transport • Diffusion – The tendency for molecules of any substance to move from a higher concentration to a lower concentration • Diffusion is an example of Passive transport – Movement of a substance across a membrane down a concentration gradient with no energy investment • Substances diffuse down their concentration gradient until equilibrium is reached Diffusion Diffusion is affected by temperature, surface area, distance and concentration Diffusion of Gases Facilitated Diffusion • Diffusion of non-lipid soluble substances across the plasma membrane through a protein channel or carrier in the membrane – From high to low concentration – Glucose transport A Comparison of Types of Diffusion Osmosis: Passive Transport • Movement of water across a selectively permeable membrane towards a higher solute concentration Figure 7.12 Water Balance of Cells • Tonicity – Concentration of salt solutions in blood and body fluids • Isotonic Solution – Concentration of solutes is equal on both sides of a cell • Hypertonic Solution – Concentration of solutes is greater outside than it is inside the cell • Hypotonic Solution – The concentration of solutes is less outside than it is inside the cell Be able to determine which way water would move when a cell is placed in each type of solution. Tonicity of a solution determines whether a cell will gain or lose water or retain the same volume. Red Blood Cells in Different Salt Concentrations Isotonic Hypertonic Hypotonic Active Transport • Moves substances against their concentration gradient • Low concentration to a high concentration • Requires energy, usually in the form of ATP • Involves carrier proteins Na+/K+ ATPase pump Secondary Active Transport Mechanisms • Antiporters carry two substances across the membrane in opposite directions. • Symporters carry two substances across the membrane in the same direction. Bulk Transport in Vesicles • Vesicle – a small spherical sac formed by budding off from a membrane • Exocytosis – Transport vesicles migrate to the plasma membrane, fuse with it, and release their contents outside a cell • Endocytosis – The cell takes in materials by forming new vesicles from the plasma membrane Exocytosis • Vesicles fuse with the plasma membrane, releasing their contents outside the cell 2 4 1 3 Endocytosis • Pinocytosis – Cell drinking • Phagocytosis – Cell eating – Macrophages (WBC) perform phagocytosis Bulk-phase Endocytosis Phagocytosis Receptor Mediated Endocytosis RECEPTOR-MEDIATED ENDOCYTOSIS • Moves substances specific for a certain cell surface receptor • Substance binds receptor on the plasma membrane, a vesicle is formed a substance is brought into the cell •Example Coat protein Receptor Coated vesicle Ligand Coated pit A coated pit and a coated vesicle formed during receptormediated endocytosis (TEMs). Coat protein Plasma membrane 0.25 µm Cytoplasm - 2 Components 1. Cytosol - intracellular fluid, surrounding the organelles - The site of many chemical reactions - Energy is usually released by these reactions. - Reactions provide the building blocks for cell maintenance, structure, function and growth. 2. Organelles - Specialized structures within the cell Cytoskeleton • Network of protein fibers that extend throughout the cytosol • Give cells their shape, internal organization and capacity to move • Dynamic system – Some components are always being assembled and disassembled Cytoskeleton • 3 types of fibers found in the cytoskeleton – Microtubules – Microfilaments – Intermediate filaments Components of Cytoskeleton • Microtubules – Composed of the globular protein tubulin – Thick hollow rods, 25nm diameter • Involved in chromosome movement in cell division • Present in cilia and flagella – Motility • Maintenance of cell shape • Organelle movement in a cell Cilia and Flagella • Cilia and flagella – Locomotor appendages of some cells – Cilia and flagella share a common ultrastructure – 9 + 2 arrangement of microtubules in a cylindrical pattern Flagella • Cell motility • Feeding • Movement of Sperm (a) Motion of flagella. A flagellum usually undulates, its snakelike motion driving a cell in the same direction as the axis of the flagellum. Propulsion of a human sperm cell is an example of flagellatelocomotion (LM). Direction of swimming 1 µm Cilia • Free surfaces of some epithelial tissues, Lining airways and Sensory hairs of human ear • Functions: Moves water over tissues, Protection • Occur in large numbers Centrosome and Centrioles • Structures involved in chromosome division during nuclear division – Are involved in forming a spindle apparatus • Centrioles are composed of microtubules Components of Cytoskeleton • Microfilaments – Composed of the protein actin – Involved in muscle contraction – Cell division, Cytokinesis – Shape of cells – Cell motility Components of Cytoskeleton • Intermediate Filaments – Composed of keratin proteins – Provide mechanical strength – Prevent excess stretching of cells – Forms the nuclear lamina Components of the Cytoskeleton Endomembrane System • Group of related organelles where lipids are assembled and amino acid chains are modified into proteins – Divides cells into compartments • Endoplasmic Reticulum • Golgi Apparatus • Vesicles Endoplasmic Reticulum • The ER membrane is continuous with the nuclear envelope • 2 types of ER – Rough Endoplasmic Reticulum, RER – Smooth Endoplasmic Reticulum, SER Figure 6.12 Rough Endoplasmic Reticulum • Surface is studded with ribosomes • RER modifies polypeptides – Attaches sugar residues – Glycoproteins • RER makes membrane phospholipids and membrane proteins • Sends modified polypeptides in vesicles to the golgi apparatus Smooth Endoplasmic Reticulum • No ribosomes on the surface • Lipids are assembled in the SER – Oils, phospholipids, steroids • Carbohydrate metabolism • Fat absorption from intestines • SER of liver inactivates wastes, detoxifies drugs and alcohols • SER of skeletal muscle, called the sarcoplasmic reticulum, stores calcium ions The RER and the SER send their proteins and lipids in transport vesicles to the golgi apparatus for refining. Golgi Apparatus • Consists of flattened membrane sacs called cisternae • Functions to put finishing touches on proteins and lipids received from the ER • Sorts and packages materials into transport vesicles – Will stay in cell or fuse with the plasma membrane Processing and Packaging Lysosomes: Digestive Compartments • Membranous sac of hydrolytic enzymes that can digest all 4 macromolecules – Enzymes work at acidic pH • Arise from the golgi apparatus 1. Lysosomes carry out intracellular digestion after Phagocytosis 2. Destroy dead or worn out cells, organelles and cell parts – Recycle what is still good Lysosomes Lysosome containing 1µm two damaged organelles 1 µm Nucleus Mitochondrion fragment Peroxisome fragment Lysosome Lysosome contains Food vacuole fuses with active hydrolytic lysosome enzymes Lysosome fuses with vesicle containing damaged organelle Hydrolytic enzymes digest food particles Hydrolytic enzymes digest organelle components Digestive enzymes Lysosome Lysosome Plasma membrane Digestion Food vacuole (a) Phagocytosis: lysosome digesting food Digestion Vesicle containing damaged mitochondrion (b) Autophagy: lysosome breaking down damaged organelle Organelles • Peroxisomes – Smaller than lysosomes – Detoxify several toxic substances such as alcohol – Abundant in the liver • Proteasomes – Continuously destroy unneeded, damaged, or faulty proteins – Found in the cytosol and the nucleus Mitochondria • Energy powerhouse of the cell • ATP synthesis occurs here (requires oxygen) – Cellular respiration • Organs with high energy needs have lots of mitochondria • Unique features: – Has its own closed circular DNA & ribosomes – Divides on its own, not with the cell – Is inherited only maternally Mitochondria • Mitochondria are enclosed by two membranes – A smooth outer membrane – An inner membrane folded into cristae Nucleus • Membrane bound structure containing DNA • Components of the nucleus include: – Nuclear envelope – Nuclear Lamina – Nuclear pores – Nucleolus – Chromosomes – Chromatin Nucleus Nuclear Envelope • Double phospholipid bilayer surrounding nucleus • Surface studded with ribosomes • Nuclear Pores span the two bilayers – Allow for movement into and out of the nucleus • Nuclear lamina – Netlike array of protein filaments that maintain shape of nucleus • Nucleolus – Dense mass of material in the nucleus – Site where ribosomal RNA is made Chromosomes and Chromatin • Chromatin – All of a cell’s DNA and the proteins the DNA is wrapped around – Uncoiled, allows regulatory proteins to attach to DNA • Beads on a string • Chromosome – 1 condensed chromatin molecule and its associated proteins – Chromosomes are made up of chromatin Packing of DNA into a Chromosome of a Dividing Cell Ribosomes • Ribosomes – Particles made of ribosomal RNA and protein – Carry out protein synthesis Cell Division • Cell division is important for many reasons – Embryonic Development – Normal Growth – Repair of damaged tissues – Replace dead or worn out cells Nuclear Division 2 types of nuclear division Mitosis Meiosis • Nuclear division in somatic • Division to produce mature cells gametes • Produces 2 daughter cells genetically identical to the parent cell • Produces 4 haploid daughter cells Chromosome Terminology • Replicated vs. unreplicated Chromosome • Sister chromatids • Centromere • Kinetechore Chromosome Duplication 0.5 µm A eukaryotic cell has multiple chromosomes, one of which is represented here. Before duplication, each chromosome has a single DNA molecule. Once duplicated, a chromosome consists of two sister chromatids connected at the centromere. Each chromatid contains a copy of the DNA molecule. Mechanical processes separate the sister chromatids into two chromosomes and distribute them to two daughter cells. Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Centrometers Sister chromatids Sister chromatids Eukaryotic Cell Terminology • Diploid • Haploid • Somatic cells • Sex cells The Cell Cycle • The cell cycle is a sequence of events in which a body cell duplicates its contents and divides in two • The cell cycle includes interphase and nuclear division, mitosis – G1, S & G2 represent Interphase • Growth of parent cell and Organelle number doubles (G1 & G2) • DNA is replicated (S) • Cell divides in mitosis (M) • Before a cell divides it MUST replicate its DNA – Mitosis begins with replicated chromosomes The Cell Cycle Interphase Mitosis • Nuclear division in somatic cells • 4 phases • Mitosis is the shortest part of the cell cycle • Mitosis is followed by cytokinesis – division of the cytoplasm • Produces 2 daughter cells genetically identical to the parent cell Phases of Mitosis • Prophase • Metaphase • Anaphase • Telophase Formation of the Mitotic Spindle • Mitotic spindle controls chromosome movement during mitosis • Begins to form in prophase • Composed of microtubules and other proteins – Assembly begins at the centrosome – Microtubules grow out from centrosome = Mitotic Spindle Mitotic Spindle • Spindle microtubules attach to kinetechore proteins located at the centromere Sister chromatids Metaphase Plate Kinetochores Overlapping nonkinetochore microtubules Kinetochores microtubules 0.5 µm Prophase • Formation of mitotic spindle and Centrosomes move to opposite poles of cell • Chromatin condenses into chromosomes • Nuclear envelope breaks down • Spindle microtubules attach to kinetechores Metaphase • Longest mitotic stage • Chromosomes line up at the metaphase plate Anaphase • • • • Shortest stage Sister chromatids separate at the centromere Chromosomes move towards opposite poles of the cell Cell elongates Telophase • Nuclei begin to form in daughter cells • Nuclear envelope forms • Chromosomes decondense • Mitosis is complete Cytokinesis in Animal Cells • Division of cytoplasm • A cleavage furrow forms at the surface of the cell where the metaphase plate was Cleavage furrow Contractile ring of microfilaments Figure 12.9 A 100 µm Daughter cells (a) Cleavage of an animal cell (SEM) Centrosome: Centrioles Pericentriolar material 1 Mitosis 6 Nucleolus Nuclear envelope Chromatin Plasma membrane Cytosol LM all at 700x (a) INTERPHASE 2 Kinetochore Centromere 5 Chromosome (two chromatids (f) IDENTICAL CELLS IN INTERPHASE joined at centromere Early Mitotic spindle (microtubules) Fragments of nuclear envelope Late (b) PROPHASE Metaphase plate 3 Cleavage furrow (c) METAPHASE 4 (e) TELOPHASE Cleavage furrow Chromosome Late Early (d) ANAPHASE Cell Division • Some cells actively divide throughout our lifetime – Skin cells, cells lining the digestive tract • Some cells divide during embryonic development and once formed, never divide again – Nerve cells, muscle cells – Are in a state called G0 Cell Cycle Checkpoints • Built in checkpoint system that can stop the cell cycle if it detects a problem – Example of problem: Chromosomes not properly separated • Checkpoints are controlled by signaling pathways Cell Cycle Checkpoints • 3 major checkpoints • G1/S, G2/M and M • G1 is the restriction point – If all is well, cycle proceeds – If not, cell enters G0 Other External Factors Important in Cell Division • Nutrients – Growth factors that stimulate cells to divide • Density of Cells – Density dependent inhibition • Crowded cells stop dividing • Anchorage Dependence – In order for normal cells to divide, they must be attached to something • Cancer cells DO NOT exhibit density dependent inhibition or anchorage dependence Loss of Cell Cycle Control • Loss of control leads to overgrowth • Transformation – process where a normal cell becomes cancerous Cancer Cell Characteristics • Are free of the body’s controls • Have chromosomal abnormalities • Have metabolic abnormalities • Loss of attachment to nearby cells – Malignancy through blood and lymph • Often grow their own blood supply Stem Cells • Stem cells are unspecialized cells that have the potential to give rise to other types of specialized cells • Differentiation – Process where a cell becomes specialized Stem Cells • 3 main populations of stem cells • Adult stem cells • Hematopoietic stem cells • Embryonic stem cells