The discovery and early study of cells progressed with the invention and improvement of microscopes in the 17th century
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A TOUR OF THE CELL How We Study Cells 1. Microscopes provide windows to the world of the cell 2. Cell biologists can isolate organelles to study their function
The minimum resolution of a light microscope is about 2 microns, the size of a small bacterium Light microscopes can magnify effectively to about 1,000 times the size of the actual specimen. At higher magnifications, the image blurs.
Techniques developed in the 20th century have enhanced contrast and enabled particular cell components to be labeled so that they stand out.
While a light microscope can resolve individual cells, it cannot resolve much of the internal anatomy, especially the organelles . To resolve smaller structures we use an electron microscope ( EM ), which focuses a beam of electrons through the specimen or onto its surface. Because resolution is inversely related to wavelength used, electron microscopes with shorter wavelengths than visible light have finer resolution. Theoretically, the resolution of a modern EM could reach 0.1 nanometer (nm), but the practical limit is closer to about 2 nm.
Isolating Organelles by Cell Fractionation Cell fractionation Takes cells apart and separates the major organelles from one another The centrifuge Is used to fractionate cells into their component parts
The principle of fractionation Tissue cells Homogenization Homogenate 1000 g (1000 times the force of gravity) 10 min Differential centrifugation Supernatant poured into next tube 20,000 g 20 min Pellet rich in nuclei and cellular debris Pellet rich in mitochondria (and chloro- plasts if cells are from a plant) Pellet rich in “microsomes” (pieces of plasma mem- branes and cells’ internal membranes) Pellet rich in ribosomes 150,000 g 3 hr 80,000 g 60 min
The Cell A cell is the smallest unit of living matter. Don’t confuse this with: atom, element, proton, etc.
Cell Theory Who? Matthias Schleiden, Theodor Schwann, Rudolf Virchow When? 1800s What does it say? All organisms are made of cells. A cell is the structural & function unit of organs. All cells come from pre-existing cells. Cells are capable of self-reproduction.
Cell Size
Types of Cells Unicellular organisms Bacteria, Protists, etc. Multicellular organisms Plants Animals Muscles, skin, nerves, liver, digestive, bones, blood, immune system, lungs, etc.
How do we observe cells? Light microscope Visible light passes through object Lens magnify image Electron microscope Scanning - surface of object Transmission - sees through objects 100,000 X to Millions magnification power
How do we know what happens in each part of the cell? Radioisotopes are used to "trace" different chemical reactions through a cell. Separate cellular structures with a blender Centrifuge material and analyze each layer.
Two basic cell types Eukaryotes (Eu = true) (kary = nucleus) Organisms whose cells contain a membrane-bound nucleus and other organelles. Prokaryotes (Pro = before) Organisms without a membrane-bound nucleus (bacteria). * These cells have genetic information, but not in a nucleus. * Evolutionists chose the prefix “pro” because they believe these evolved before others.
Prokaryotic Cells Organisms with prokaryotic cells are called “prokaryotes” Prokaryotes have no true nucleus or organelles. Have a single strand of “ looped ” DNA Most prokaryotes are single-celled microscopic organisms.
Eukaryotic Cells Organisms composed of eukaryotic cells are called “eukaryotes” Have a membrane bound nucleus which contains the cell’s DNA Some eukaryotes are one-celled organisms All multicellular organisms are eukaryotes Have organelles , each of which is surrounded by (or bound in) a “plasma membrane”
Some Example Prokaryotes Bacillus-shaped bacterium Coccus-shaped bacterium Spirillum -shaped bacterium
Prokaryotes vs. Eukaryotes (1) Size Prokaryotes ≤ 10 µm example: Bacteria & Archea Eukaryotes ≥ 10 µm example: Protista, Fungi, Plants, Animals Complexity Prokaryotes – simple Eukaryotes – complex Location of chromosomes Prokaryotes – free in cytosol Eukaryotes – within a membrane-bound nucleus Flagellar mechanisms differ
Prokaryotes vs. Eukaryotes (2) Very simple cells Always single-celled No nucleus DNA arranged in one single loop Found only in kingdom Monera (bacteria) Complex cells Can be single-celled or multicellular Have a nucleus DNA arranged in many separate strands Found in Animal, Plant, Protists, and Fungi kingdoms
Prokaryotic Cells Have no membrane-bound organelles Include true bacteria On earth 3.8 million years Found nearly everywhere Naturally in soil, air, hot springs
Viruses Viruses contain DNA or RNA & a protein coat Some are enclosed by an envelope Most viruses infect only specific types of cells in one host Host range is determined by specific host attachment sites and cellular factors
Prokaryotic bacteria cells surrounding a eukaryotic cell (possibly a white blood cell?)
Eukaryotes Prokaryotes Protists, fungi, plants, animals Bacteria, archaea Typical organisms 10 – 100 m m 1 - 10 m m Typical size Real nucleus w/ double membrane Nucleoid, no real membrane Type of nucleus Linear molecules (chromosomes) with histone proteins Circular (usually) DNA RNA synthesis inside the nucleus, protein synthesis in cytosol Coupled in cytoplasm RNA/protein synthesis Comparison between prokaryotes & eukaryotes (1)
Eukaryotes Prokaryotes 60S + 40S 50S + 30S Ribosomes Highly structured by endomembraes and a cytoskeleton Very few structures Cytoplasmic structure Flagella & cilia made of tubulin Flagella Cell movement One to several dozen None Mitochondria Algae & plants None Chloroplasts Comparison between prokaryotes & eukaryotes (2)
Eukaryotes Prokaryotes Single cells, colonies, higher multicultural organisms w/ specialized cells Usually single cells Organization Mitosis & meiosis Binary fission (simple division) Cell division Comparison between prokaryotes & eukaryotes (3)
Eukaryotic Cell
Cell Structure & Function (1) Bacteria
Cell Structure & Function (2) Typical Plant
Cell Structure & Function (3) Generic Animal Cell
Eukaryotic Cells Structure (1) Have numerous internal structures Various types & forms Plants, animals, fungi, protists Multicellular organisms
Eukaryotic Cells Structure (2) The cell consists of two main compartments: The nuclear The cytoplasmic The nucleus contains the genetic information that regulates the structure and function of all eukaryotic cells The cytoplasm contains numerous cellular organelles, which perform specific functions
Plant & Animal Cells (1) Similarities Both constructed from eukaryotic cells Both contain similar organelles Both surrounded by cell membrane
Plant & Animal Cells (2) Differences Plants have Cell wall – provides strength & rigidity Have chloroplasts, photosynthetic site Large vacuoles Animals have Other organelle not found in plants (lysosomes formed from Golgi) Centrioles, important in cell division
Nucleus The nucleus is separated from the cytoplasm by the nuclear envelope
Nucleus Structure
Nucleus: DNA stored here. The Control Center Nuclear envelope : membrane surrounding the nucleus Nuclear pores : open portals of communication between the nucleus & cytoplasm Chromatin : condensed DNA Chromosome : very tightly packed DNA Nucleolus : dense region of chromatin
DNA proteins DNA is associated with two major types of proteins: The histone and nonhistone chromosomal proteins The histones are primarily structure molecules that pack DNA into chromatin fibers The nonhistones include proteins that carry out one of the most important cellular functions, the regulation of gene activity
Chromosomes DNA molecule, with its associated histone and nonhistone proteins, is a chromosome There are five classes of histone proteins: H1 H2A H2B H3 H4
Nucleosomes H2A, H2B, H3, and H4 are called core histones because they form a beadlike core structure around which DNA wraps to form nucleosomes . H1 is called the linker
Human Chromosomes The entire complement of 46 chromosomes in a human cell, has a total length of about 1 meter
Nucleolus (Nucleoli) The RNA of ribosomes is synthesized from genes in the nucleolus No membranes separate nucleoli from the surrounding chromatin in the nucleus
Protein-encoding gene Each DNA segment containing the information in a protein constitutes a gene The information in a Protein-encoding gene is copied into a messenger RNA (mRNA) molecules that moves to the cytoplasm through the pores of the nuclear envelop In the cytoplasm, mRNA molecules are used by ribosomes as directions for the assembly of proteins DNA -----------> mRNA -----------> Protein (enzymes)
RNA types mRNA rRNA tRNA Ribosomes : protein factories Rough ER : make proteins (studded with ribosomes) Smooth ER : make lipids, modify proteins made in RER
Mitochondria & Chloroplast: Power Stations of the cell
Mitochondria (1) The mitochondria major role is ATP production in the eukaryotic cell These are mobile and flexible organelles, although in some cells they tend to stay in a fixed position Mitochondria are also self-reproducing, they have their own circular DNA
Mitochondria (2) Generate cellular energy in the form of ATP molecules ATP is generated by the systematic breakdown of glucose = cell respiration Also, surrounded by 2 membrane layers Contain their own DNA! A typical liver cell may have 1,700 mitoch. All your mitoch. come from your mother
Inner Membrane and matrix (3) Electron transport system
Oxidative phosphorylation (4) Inner Membrane ATP synthase Electron transport system I III IV H + H + H + H + 3H + 3H + 3 ADP + 3 P i 3 ATP NADH H + 2e- H +
Mitochondria Chloroplasts Compartments 2 3 pH 7 – 8 5 - 8 Metabolic Sites Matrix : TCA cycle, ATP synthesis ETC : 3H + pumps Stroma : Calvin cycle & ATP synthesis ETC : 1H + pump Substrates Oxidizes glucose, other metabolites to make ATP Light Rxn : use energy from light to synthesize NADPH & ATP Dark Rxn : use CO 2 & H 2 O & NADPH & ATP to synthesize glucose Wastes CO 2 & H 2 O O 2
Chloroplast
Mitochondria
Endoplasmic reticulum (1) Rough endoplasmic reticulum smooth endoplasmic reticulum are connected and are continuous with the nuclear envelope
Rough endoplasmic reticulum (2) It is rough because imbedded in the membrane are ribosomes the site of the synthesis of secretory proteins The rough ER is also the site for the synthesis of membrane Enzymes synthesize phospholipid that forms all the membranes of the cell Ribosomes in the rough ER synthesize protein that then are converted to glycoprotein and packaged in transport vesicles for secretion
Smooth endoplasmic reticulum (3) The smooth ER is the site for the synthesis of lipids, phospholipids, and steriods Note that the production of steriod hormones is tissue specific For example, it is the smooth ER of the cells of the ovaries and testes that synthesize the sex hormones The smooth ER of the liver has several additonal functions
Smooth endoplasmic reticulum (4) Enzymes in the smooth ER regulate the release of sugar into the bloodstream Other enzymes break down toxic chemicals As the liver is exposed to additional doses of a drug the liver increases the amount of smooth ER to handle it It then takes more drug to get past the detoxifiying ability of the liver Finally the smooth ER functions to store calcium ions
Golgi apparatus (1) The Golgi apparatus, like the ER, is a series of folded membranes It functions in processing enzymes and other products of the ER to a finished product It is the source of the production of lysosomes Receives proteins & lipids in membrane-bound vesicles from ER Modifies those proteins & lipids Sorts and ships the proteins & lipids away in membrane-bound vesicles
Golgi complex vesicles from ER vesicles leaving Golgi complex
Lysosomes These are membrane bound vesicles that harbor digestive enzymes The membrane of a lysosome will fuse with the membrane of vacuoles releases these digestive enzymes to the interior of the vacuole to digest the material inside the vacuole
Vacuoles These are membrane-bound sacs that have many different functions The central vacuole of a plant cell serves as a large lysosome It may also function in absorbing water. The central vacuoles of flower petal cells may hold the pigments that give the flower its color
Endomembrane system This section reviews the endomembrane system which encludes the nuclear envelope, the rough and smooth ER, the Golgi apparatus, lysosomes and vacuoles
Ribosomes (1) Ribosomes assemble amino acid monomers into polypeptide chains Associated with the ER Composed of RNA and proteins 0.5 micrometers smooth endoplasmic reticulum vesicles ribosomes rough endoplasmic reticulum 0.5 micrometers
Ribosome Assembly/Structure (2) If individual proteins and rRNAs are mixed, functional ribosomes will assemble Structures of large and small subunits have been determined in 2000/2001 Growing peptide chain is thought to thread through the tunnel during protein synthesis
Eukaryotic ribosomes (3) Mitochondrial and chloroplast ribosomes are quite similar to prokaryotic ribosomes, reflecting their supposed prokaryotic origin Cytoplasmic ribosomes are larger and more complex, but many of the structural and functional properties are similar
Mechanics of protein synthesis All protein synthesis involves three phases: initiation, elongation, termination Initiation involves binding of mRNA and initiator aminoacyl-tRNA to a small subunit, followed by binding of a large subunit Elongation: synthesis of all peptide bonds - with tRNAs bound to acceptor (A) and peptidyl (P) sites Termination occurs when "stop codon" reached
Eukaryotic cells has a meshwork of tiny fibers that support the structure. This network is the cytoskeleton. Three types of fibers exist. Microfilaments are solid helical rods composed of the protein actin. There is a twist double chain of actin molecules that make up microfilaments. These are found in cells that must contract such as muscle cells. Intermediate filaments are variable but in general are ropelike structures made of twisted filaments of fibrous proteins. These function in bearing tension and anchoring organelles. Microtubles are straight, hollow tubes composed of proteins called tubulins. These anchor organelles and provide tract along which organelles may move. They also make up flagella and cilia. Cytoskeleton
These are found on cells, such as protists, that are motile. Cilia are short and numerous. Longer less numerous appendages are flagella. These are composed of a core of microtubules wrapped in an extension of the plasma membrane. It is sufficient to know that Energy is required to move the cilia or flagella in a whiplike motion to propel the cell. Cilia and flagella
Cells are held tightly together is higher organisms. There is also a considerble amount of cell communication for lack of a better term. Cell junctions are structures that hold cells together. There are three types. Tight junctions bind cells together forming a leakproof sheet. Anchoring junctions attach adjacent cells or cells to an extracellular matrix (the substance in which tissues cells are embedded. These are leaky compared to tight junctions. Communicating junctions are channels between similar cells. Plasmodesmata are passages between adjacent plant cells that allow material to go from one cell to the next. Communication junctions fulfill the same role between animal cells. Cell surfaces
Cytoskeleton : provides structure and Support for the cell. Also provides a Scaffolding for vesicle transportation
Functions Eukaryotes Prokaryotes Organelle Plant cells Animal cells Prokaryotes Protects & shapes the cell + _ + Cell wall Selective barrier consisting of bilayers of phospholipids, proteins, & CHO + + + Plasma membrane Protein synthesis, formed in nucleolus + + + Ribosome Rapid Review (1)
Functions Eukaryotes Prokaryotes Organelle Plant cells Animal cells Prokaryotes Lipid synthesis, detoxification, CHO metabolism, no ribosomes on cytoplasmic surface + + _ Sooth ER Synthesizes proteins to secrete or send to plasma membrane. Contains ribosomes on cytoplasmic surface + + _ Rough ER Modifies lipids, proteins, etc & sends them to other sites in the cell + + _ Gogli Rapid Review (2)
Functions Eukaryotes Prokaryotes Organelle Plant cells Animal cells Prokaryotes Powerhouse of cell; host major energy-producing steps of respiration + + _ Mitochondria Contains enzymes that digest organic compounds; serves as cell’s stomach + + _ Lysosome Control center of cell. Host for transcription, replication & DNA + + _ Nucleus Rapid Review (3)
Functions Eukaryotes Prokaryotes Organelle Plant cells Animal cells Prokaryotes Breakdown of FA, detoxification of alcohol + + _ Peroxisome Site of photosynthesis + _ _ Chloroplast Storage vault of cells + (large) + (small) _ Vacuole Rapid Review (4)
Functions Eukaryotes Prokaryotes Organelle Plant cells Animal cells Prokaryotes Consists of microtubules (cell division, cilia, flagella), microfilaments (muscles), & intermediate filaments (reinforcing position of organelles + + _ Cytoskeleton Part of microtubule separation apparatus that assists cell division _ + _ Centrioles Rapid Review (5)
Function of cell membranes Compartmentalization of tissues Regulation of cell contents Provides surface for enzymes, receptors, recognition, etc.
Phospholipids: the “backbone” of the membrane Cartoon of a phospholipid molecule * both polar and non-polar regions Fatty acids Glycerol plus polar side group
Water molecules are polar Structure of water and the Cartoon version Water is a dipole O H H + + d d/2 d/2 +
Water is a good solvent for polar molecules and ions Na + Cl - - + - + - + - + - + - + - + Hydration Shells - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - + - +
Phospholipids Cartoon of a phospholipid molecule Polar head (Hydrophilic- likes water) Non-polar tail (Hydrophobic- hates water)
Oil/water partition: the “kitchen” experiment MIX OIL WATER AND TEST SUBSTANCE WAIT OIL WATER
Mixing phospholipids and water: spontaneous self-organization
Mixing phospholipids and water: spontaneous self-organization
Mixing phospholipids and water: spontaneous self-organization
Mixing phospholipids and water: spontaneous self-organization
Micelle Sheet
The membrane is fluid
The membrane is fluid
The membrane is fluid
The membrane is fluid
Cholesterol sits between fatty tails
The fluid-mosaic model
Channels and carriers are needed to get ions across the bilayer
Channels and carriers are needed to get ions across the bilayer
Stem Cells (2) Research on stem cells is advancing knowledge about: how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms This promising area of science is also leading scientists to investigate the possibility of cell-based therapies to treat disease, which is often referred to as regenerative or reparative medicine
What are stem cells and why are they important? (3) Stem cells have two important characteristics that distinguish them from other types of cells: First, they are unspecialized cells that renew themselves for long periods through cell division The second is that under certain physiologic or experimental conditions, they can be induced to become cells with special functions such as: the beating cells of the heart muscle or the insulin-producing cells of the pancreas
Stem Cells (4)
Kinds of stem cells (5) Scientists primarily work with two kinds of stem cells from animals and humans: embryonic stem cells and adult stem cells, which have different functions and characteristics
Stem cells are important for living organisms (5) Stem cells are important for living organisms for many reasons. In the 3 to 5 day old embryo, called a blastocyst, a small group of about 30 cells called the inner cell mass gives rise to the hundreds of highly specialized cells needed to make up an adult organism. In the developing fetus, stem cells in developing tissues give rise to the multiple specialized cell types that make up the heart, lung, skin, and other tissues
In some adult tissues (6) In some adult tissues, such as: bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost: through normal wear and tear, injury, or disease
Hemopoietic cells (7) The basis of haemopoiesis is a small population of self-replicating stem cells, which ultimately can generate all types of blood cells. The process of haematopoiesis is controlled by a group of at least 11 growth factors. Three of these glycoproteins initiate the differentiation of macrophages from uni- and bipotential progenitor cells in the bone marrow.
Macrophages and monocytes (8) Their development takes in the bone marrow and passes through the following steps: stem cell committed stem cell monoblast promonocyte monocyte (bone marrow) monocyte (peripheral blood) macrophage (tissues)
Blood monocytes (9) The blood monocytes are young cells that already possess migratory, chemotactic, pinocytic and phagocytic activities, as well as receptors for IgG
Macrophages (10) Macrophages can be divided into normal macrophages and inflammatory macrophages. Normal macrophages includes macrophages in connective tissue . Inflammatory macrophages are present in various exudates. Phagocytes and since they are derived exclusively from monocytes they share similar properties.
Phagocytes (11) Phagocytes are cells which ingest particles. The process of eating particles is called "phagocytosis," a process which is one of the distinguishing features of eukaryotic cells,
Phagocytes (12)
How cells divide: Cell cycle
Cells must be able to grow & divide New cells must contain complete copies of the entire set of chromosomes and all their DNA A Cell’s lifetime of growth & division can be referred to as a Cell Cycle Cell cycle
Cell cycle Includes not only cell division, but also the intervening time period when cells are not dividing...
Interphase Composed of G1, S & G2 phases Interphase includes everything except Mitosis
Interphase G1: gap phase between Mitosis & S S phase: DNA replication G2: gap phase between S & Mitosis
Mammalian cell cycle G1: Highly variable, Absent in rapidly dividing cells, long in slow-growing cells S: 6-8 hours G2: 3-6 hours M: 1-2 hours
G1 arrested cells An important control point in cell cycle holds cells in G1 Cells can remain indefinitely in G1 Such cells are said to reside in a G state, a cell cycle holding point G Cells may re-enter the normal cell cycle if given conditions suitable for growth
The S phase Each Chromosome replicates to form 2 Chromatids . Replicated chromatids are joined together at their centromeres
1. Prophase Three things visibly occur Chromosomes condense (shorten) Centrosomes migrate to the poles while producing spindle fibers Nuclear membrane fragments
2. Metaphase Chromosomes are moved by growing spindle fibers to the equator of the cell (metaphase plate) Centrosomes are at the poles, nuclear membrane is gone
3. Anaphase Anaphase movement in two parts : Chromosomes move toward opposite poles Poles themselves move apart Anaphase movement uses ATP
4. Telophase Chromosomes unfold and disperse (no longer condensed) Spindle dissassemble Nuclear membrane Reforms Gene activity resumes
Cytokinesis Actual cell division stage Cytokinesis (division of the cytoplasm) may occur
SEXUAL(MEIOSIS) Figure 14.32. Comparison of meiosis and mitosis . Both meiosis and mitosis initiate after DNA replication, so each chromosome consists of two sister chromatids. In meiosis I, homologous chromosomes pair and then segregate to different cells. Sister chromatids then separate during meiosis II, which resembles a normal mitosis. Meiosis thus gives rise to four haploid daughter cells . Fuente: Cooper, 2000
VIRAL LIFE CYCLE ATTACHMENT PENETRATION HOST FUNCTIONS ASSEMBLY (MATURATION) Transcription REPLICATION RELEASE UNCOATING Translation MULTIPLICATION Click after each step to view process