Foundations - Cells, organelles and cell boundaries

Introduction

Dr Mark Hill

This lecture is currently being updated for 2018 as an online self-directed learning exercise.

Please work through the following 7 online content sections each consisting of a lecture concept explained in a 5 minute video. When you have finished the entire series then attempt the online Moodle quiz.

Lecture pages

About each page

Introduction to cells and sizes Prokaryotes Viruses and prions Plasma Membrane Compartments Components Specialisations

Each page has the same components: Video - at the top of each page and each is about 5 minutes in length. Watch this first by clicking the play arrow to begin. Links - to all the other online pages. Directly under the video. Terms - a simplified glossary of terms used in the video content. Text version - content shown in video. This includes images, videos and links to online cell biology textbooks.

Draft - this online lecture is currently in 2020 draft status. This notice removed when completed.

Cells	Organelles and Boundaries
Our cells are dynamic	Our cells contain many membrane bound compartments

Lecture Archive

Below is the previous lecture as it was presented in "face to face format" in 2017. Lecture: 2017 | 2016 Lecture PDF | 2016 | 2015 | 2014 | 2013 14 pages PDF | 2012 Page | 2012 14 pages PDF The 2 major classes of cells are defined by the presence of a nucleus; Eukaryotic and absence of a nucleus Prokaryotic. Eukaryotes can be further divided into unicellular (only one cell, like prokaryotes) and multicellular (like us) organisms. A major difference between eukayotes and prokaryotes is the presence of physical compartments (membrane bound) and organelles within the cell. These compartments allow the separation/specialization of processes within the cell. There also exist within each of these physical compartments, functional compartments where specific processes may occur or are restricted. This lecture is also an introduction to cell compartments and describes the structure of membranes forming these compartments. About Human Body Human Cells 210+ cell types in body total number of estimated cells in the body - 1013 (American Ten trillion/British Ten billion) Flora bacteria, fungi and archaea found on all surfaces exposed to the environment skin and eyes, in the mouth, nose, small intestine most bacteria live in the large intestine 500 to 1000 species of bacteria live in the human gut total number of estimated flora ten times as many bacteria 1014 (American One hundred trillion/British One hundred billion) Cell Sizes 1000 micron (1mm) diameter - frog or fish egg are the largest individual cells easily visible, 100 micron diameter - human or sea urchin egg 30 x 20 micron - plant cells 20 micron diameter - typical somatic cell 2 x 1 micron - bacteria A micron or micrometre is one millionth of a metre. (1 x 10-6) Cell History   Background only, you do not need to know the details. Cork Bark by Robert Hooke 1665 Robert Hooke (1635-1703) - used early microscopes to view cork tree bark, first to use the term CELL. Robert Brown 1825 - identified nuclei in plant cells. Theodor Schwann (1810 - 1882) - together with Matthias Schleiden (plants) developed the cell theory in 1839 All organisms consist of one or more cells. The cell is the basic unit of structure for all cells. All cells arise only from preexisting cells. Divisions of Life Prokaryotic bacteria and archaea (single-celled microorganisms previously called archaebacteria) no cell nucleus or any other organelles within their cells organisms that can live in extreme habitats Archaea Eukaryotic File:Leukocyte phagocytosis of yeast cell nucleus plants, animals, fungi, protists Unicellular and Multicellular Unicellular All prokaryotes and some eukaryotes (Yeast + budding, non-budding) Protozoa + classified by means of locomotion: flagellates, amoeboids, sporozoans, ciliates + often "feed" on bacteria Multicellular Eukaryotes - Plants and Animals Allowed development of specialized cells, functions and tissues Karyote from the Greek, Karyose = kernel, as in a kernel of grain; referring to the presence or absence of a nucleus. Prokaryote Prokaryote cell cartoon Escherichia coli Micrococcus luteus bacteria Bacteria shape (morphology) Bacterial morphologies evolutionarily arose first (3.5 billion years ago) Evolution of Cells bacteria are biochemically diverse and smaller, approx 2 x 1 micron (1x10-6 m) simple structure, classified by shape (rod-shaped, spherical or spiral-shaped) some prokaryotic cells have also been shown to have a "cytoskeleton", which is different from eukaryotic cells. some bacteria are highly motile  ‎‎Bacteria Motility Page | Play Not all bacteria are dangerous or disease causing - The adult human in addition bacteria to the skin surface and lining of the respiratory/digestive tract, also has intestines contains trillions of bacteria made up from hundreds of species and thousands of subspecies) Prokaryotes Cell Wall Prokaryote cell cartoon Bacterial Shape - Bacterial shapes and cell-surface structures Bacterial Membranes - A small section of the double membrane of an E. coli bacterium Bacterial outer membranes - outer membrane contains porins Bacterial cell walls - Bacterial cell walls Gram-negative bacteria surrounded by a thin cell wall beneath the outer membrane Gram-positive bacteria lack outer membranes and have thick cell walls (MH - note that some unicellular eukaryotes can also have a cell wall) Antibiotics - inhibit either bacterial protein synthesis or bacterial cell wall synthesis Antibiotic targets Gram-positive and Gram-negative bacteria Bacterial Replication  ‎‎Bacteria Division Page | Play  ‎‎Bacteria Division Page | Play Links: Molecular Biology of the Cell Figure 25-4. Bacterial shapes and cell-surface structures | Figure 11-17. A small section of the double membrane of an E. coli bacterium | Medical Microbiology Figure 2-6. Comparison of the thick cell wall of Gram-positive bacteria with the comparatively thin cell wall of Gram-negative bacteria Prokaryote Mycoplasmas smallest self-replicating organisms, smallest genomes (approx 500 to 1000 genes) spherical to filamentous cells, no cell walls surface parasites of the human respiratory and urogenital tracts Mycoplasma pneumoniae infect the upper and lower respiratory tract Mycoplasma genitalium a prevalent sexually transmitted infection Mycoplasma hyorhinis found in patients with AIDS Links: The Cell- A Molecular Approach | Table 1.1. Prokaryotic and Eukaryotic Cells | Antibiotic Inhibitors of Protein Synthesis | Molecular Cell Biology Figure 12-6. DNA replication and cell division in a prokaryote | Biochemistry Figure 28.15. Transcription and Translation two processes are closely coupled in prokaryotes, whereas they are spacially and temporally separate in eukaryotes. Biological (but not alive) Virus single compartment, no membranes not alive, infects living cells (Latin, virus = toxin or poison) unable to grow or reproduce outside a host cell Infect different hosts (animal, plant and bacterial) Classified - RNA or DNA viruses; double or single stranded Virion - virus particle, the infective agent, contains the genetic material, DNA or RNA within a protective protein coat (capsid) Bacteriophage - A virus that infects bacteria Zika virus Herpes virus Nature 3Mar14 - Giant virus resurrected from 30,000-year-old ice Links: MCB - Viruses: Structure, Function, and Uses | MCB - Retroviral life cycle | NPR - Virus Infection | Foodbourne Illness Prion an infectious prion protein, no compartments, no membrane not alive, misfolded normal protein (three-dimensional structure), can form aggregates Creutzfeldt-Jacob disease (CJD) and Kuru a human neural prion disease Variant Creutzfeldt-Jakob disease (vCJD) Brain caused by consumption of food of bovine origin contaminated with the agent of Bovine Spongiform Encephalopathy (BSE). Bovine spongiform encephalopathyvery (BSE) in cattle, "mad cow disease" Scrapie in sheep Links: Creutzfeldt-Jakob disease | Molecular Biology of the Cell Figure 6-89. Protein aggregates that cause human disease | Prions Are Infectious Proteins | Gene Reviews Prions | Neuroscience Prion Disease Variant Creutzfeldt-Jakob disease (vCJD) Brain Biological Levels Cells can be "broken down" into smaller and smaller constituent "parts" Whole cell Organelles - nucleus, mitochondria, endoplasmic reticulum, Golgi Components - membrane, channels, receptors Biological polymers - DNA, RNA, Protein, sugars, cellulose (chains of molecules, consisting of monomer subunits) Organic molecules - nucleotides, amino acids, carbohydrate (monomer subunits) Typical cell membrane bound compartments Eukaryotic Cell Organelles Fundamental concept - all eukaryotic cells (some specialized exceptions) Membrane bound (enclosed) - specialized part of a cell that has its own particular function forms "compartments" within the cell Plasma Membrane Images The cell membrane (plasma membrane or plasmalemma) encloses or covers all cell types and is 7 nanometers thick (1000 times smaller than the RBC). Here are some different ways of looking microscopically at membranes. Light Micrograph Scanning Electron Micrograph Transmission Electron Micrograph Links: Membrane Images | RBC membrane | Serial Scanning Electron Microscopy Compartments Physical Compartments - membrane bound Nucleus, Cytoplasm, Organelles - cell nomenclature based upon presence or absence of these compartments (eukaryotic, prokaryotic). Functional Compartments - spatial localization for targeting, activation and inactivation, signaling. Major Cellular Compartments Proposed model for nucleus organelle membrane evolution Nucleus (nuclear) - contains a single organelle compartment Cytoplasm (cytoplasmic) - contains many organelle compartments Organelle Number/Volume How many organelles? How much space within the cell do they occupy? Are all the cells the same? Take a typical mammalian liver cell.... Liver Structure Table 12-1. Relative Volumes Occupied by the Major Intracellular Compartments in a Liver Cell (Hepatocyte) Table 12-2. Relative Amounts of Membrane Types in Two Kinds of Eucaryotic Cells Compartments are Dynamic - Movies showing flexibility of membranes and their changing shape and size. Nuclear Compartment Nucleus cartoon Nuclear matrix - consisting of Intermediate filaments (lamins) Nucleoli (functional compartment - localised transcription DNA of RNA genes) Chromosomes (DNA and associated proteins) (MH - you will not see chromosomes in interphase nuclei only during mitosis) Cytoplasmic Compartment Mitochondria Cytoplasmic Organelles - Membrane bound structures (Endoplasmic reticulum, golgi apparatus, mitochondria, lysosomes, peroxisomes, vesicles) Cytoskeleton - 3 filament systems Cytoplasmic “structures” - Ribosomes (translation) Proteins - Receptors, signaling, metabolism, structural Viruses, bacteria, prions Functional compartments (you cannot see a membrane) occur in nucleus, cytoplasm, in organelles and outside organelles signaling, metabolic reactions, processing genetic information, cytoskeleton dynamics, vesicle dynamics Membrane Functions EM - Cell (Plasma) and Organelle Membranes Cell membrane (Plasma membrane , plasmalemma) encloses or covers all cell types. Regulation of transport, Detection of signals, Cell-cell communication, Cell Identity Internal membranes form compartments, Allow “specialisation” - metabolic and biochemical, Localization of function Membrane Components Model of Cell (plasma) membrane structure phospholipids, proteins and cholesterol first compartment formed prokaryotes (bacteria) just this 1 compartment eukaryotic cells many different compartments Phospholipids Phospholipid Orientation Membranes contain phospholipids, glycolipids, and steroids The main lipid components include: phosphatidylcholine (~50%), phosphatidylethanolamine (~10%), phosphatidylserine (~15%), sphingolipids (~10%),cholesterol (~10%), phosphatidylinositol (1%). Phospholipid Orientation A liposome (lipid vesicle) is a small aqueous compartment surrounded by a lipid bilayer. A micelle is a small compartment surrounded by a single lipid layer. Links: MBoC - Three views of a cell membrane | MBoC - Phospholipid structure and the orientation in membranes Membranes History Background only, you do not need to know the details. 1890 Charles Overton - selective permeation of membranes, non-polar pass through (lipid soluble), polar refractory 1905 Irving Langmuir - lipids faced with heads towards water away from organic solvents 1925 Gorter and Grendel - monolayer of lipid isolated from rbc 1930-40 Danielle-Davson - Proteins coat a bilayer with polar “pores” 1960s Robertson - Modification with glycoprotein on one side, therefore asymmetric 1972 Singer and Nicholson - proteins “floating” within lipid bilayer like a “liquid” surface 1975 Unwin and Henderson - integral membrane proteins, glycoprotein carbohydrate groups on outer surface 1997 Simons - cholesterol to form "rafts" that move within the fluid bilayer PMID 9177342 Membrane Proteins Model of membrane proteins and dimensions Links: image - Membrane model A,B,C | image - Membrane model dimensions | image - Membrane model outside | image - Membrane model inside 20-30% of the genome encodes membrane proteins PMID 9568909 Proteins can be embedded in the inner phospholipid layer, outer phospholipid layer or span both layers Some proteins are folded such that they span the membrane in a series of “loops” Membrane Protein Functions - transport channels, enzyme reactions, cytoskeleton link, cell adhesion, cell identity Links: Figure 17-21. Topologies of some integral membrane proteins synthesized on the rough ER Membrane Glycoproteins - Glycoproteins are proteins which have attached carbohydrate groups (sugars) produce these proteins go through a very specific cellular pathway of organelles (secretory pathway) reach the cell surface where they are either secreted (form part of the extracellular matrix) or are embedded in the membrane with the carbohydrate grouped on the outside surface (integral membrane protein) Two major protein transmembrane structures: α-helical - ubiquitously distributed; β-barrel - outer membranes of Gram-negative bacteria, chloroplasts, and mitochondria. Membrane Cholesterol small molecule regulates lipid mobility (MH - see rafts) embedded between the phospholipid molecules, different concentrations in different regions of plasma membrane lateral organization of membranes and free volume distribution may control membrane protein activity and "raft” formation Note - bacterial membranes (except for Mycoplasma and some methylotrophic bacteria) have no sterols, they lack the enzymes required for sterol biosynthesis. Model of Cell (plasma) membrane structure Links: MBoC Figure 10-9. Cholesterol in a lipid bilayer Bacterial Membranes Gram positive bacteria Gram Negative inner membrane is the cell's plasma membrane do not retain dark blue dye used in gram staining Bacteria with double membranes (Example: Escherichia coli, Salmonella, Shigella,) Gram Positive because they do retain blue dye, thicker cell walls single membrane comparable to inner (plasma) membrane of gram negative bacteria Bacteria with single membranes (Example: staphylo-cocci and streptococci) (Named after - Hans Christian Gram (1853–1938), a Danish scientist.) Membrane Features Fluidity Neutrophil activation membrane reorganisation Membranes can demonstrate both high fluidity and fixed domains (regions)??? Experiments wit fusion of 2 cells, FRAP membrane domains (polarized cells) - epithelia have apical, basal and lateral domains Links: MBoC - Membrane Fluidity movie FRAP | MBC - Membrane Fluidity| Specializations plasma membrane cytoskeleton different directly under membranes adhesion complexes absorbtive and secretory synaptic junctions Adhesion Specializations A series of different types of proteins and cytoskeleton associations forming different classes of adhesion junctions Desmosomes ( = macula adherens) Adherens Junctions ( = zonula adherens) Septate Junctions Tight Junctions Gap Junctions Transport Three major forms of transport across the membrane Passive - Simple diffusion Facilitated - transport proteins Active - transport proteins for nutrient uptake, secretion, ion balance Ion Channels Cell potassium channels membrane phospholipid impermeable to ions in aqueous solution protein channels permit rapid ion flux 1960’s structure and function, ionophores (simple ion channels) 75 + different ion channels, opening/closing, “gating” of ions "Sometimes you eat the bacteria and sometimes... well, he eats you" Additional Information The material below is not part of the actual lecture and is provided for background information and student self-directed learning purposes. Cell Apoptosis - programmed cell death membrane "blebbing" encloses cellular component fragments do not stimulate inflammatory response, easy removal by macrophages. Link: Time-lapse movie of human HeLa cells undergoing apoptosis | Example of early apoptotic blebbing | PMID 16129889 | PMID 18073771 Cystic Fibrosis - membrane transport disease 1989 Collins (US), Tsui and Riordan (Canada) Chloride channel - protein mutation point mutant, folded improperly, trapped and degraded in ER Ion Channel Types 3 rapid + 1 slow gate (gap junction) Voltage-gated - propogation of electrical signals along nerve, muscle Ligand-gated - opened by non-covalent, reversible binding of ligand between nerve cells, nerve-muscle, gland cells Mechanical-gated - regulated by mechanical deformation Gap junction - allow ions to flow between adjacent cells open/close in response to Ca2+ and protons Textbook References Here are some Cell Biology online textbooks for further general reading on these topics. Molecular Biology of the Cell: Some Important Discoveries in the History of Light Microscopy | The evolution of higher animals and plants (Figure 1-38) | From Procaryotes to Eucaryotes | From Single Cells to Multicellular Organisms | Some of the different types of cells present in the vertebrate body | Chapter 10 - Membrane Structure | Three views of a cell membrane | The evolution of higher animals and plants (Figure 1-38) | From Procaryotes to Eucaryotes | From Single Cells to Multicellular Organisms | Some of the different types of cells present in the vertebrate body Molecular Cell Biology: The Architecture of Cells | Microscopy and Cell Architecture | Organelles of the Eukaryotic Cell | Biomembranes The Cell- A Molecular Approach: An Overview of Cells and Cell Research | Cell Mmebranes | Tools of Cell Biology Search Online Textbooks "prokaryote" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach "eukaryote" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach "cell compartments" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach "cell membrane" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach Historic Papers Below are some example historical research finding related to cell membranes from the JCB Archive and other sources. 1957 The invention of freeze fracture EM and the determination of membrane structure Russell Steere introduces his home-made contraption for freeze fracture electron microscopy (EM), and Daniel Branton uses it to conclude that membranes are bilayers. 1971 Spectrin is peripheral S. Jonathan Singer, Garth Nicolson, and Vincent Marchesi use red cell ghosts to provide strong evidence for the existence of peripheral membrane proteins. 1992 Lipid raft idea is floated Gerrit van Meer and Kai Simons get the first hints of lipid rafts based on lipid sorting experiments.

Draft - this online lecture is currently in 2020 draft status. This notice removed when completed.