Pre-Medicine Program - Cell Compartments and Membranes

From CellBiology

Cell Membranes and Compartments

About Today's Class

Dr Mark Hill


Lecture Slides 2017

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Pre-Medicine Program - Membranes and Compartments 
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Introduction

Eukaryotic Cell Physical Compartments

A major difference between eukayotes and prokaryotes is the presence of physical compartments (membrane bound) 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 too. This lecture is an introduction to compartments within the cell and membranes. The key components are: cell compartments, membrane structure, membrane models, membrane specializations.


  • Medications act on cells or tissues and can mimic, block or activate metabolic or signalling pathways.
  • Membranes form compartments and are involved in signalling
    • Insulin, glucagon, hormone and neurotransmitter receptors are embedded in the plasma membrane.
  • Nutrients - Cells transport nutrients across cell membranes into specific compartments for use.
    • Glucose transporter embedded in the plasma membrane.
  • Waste - Cells transport waste across cell membranes into extracellular specific compartments for excretion.

Objectives

  • Understand the concept of separate intracellular spaces
  • Understand the structure of membranes
  • Understand the difference between physical and functional compartments
  • Brief understanding of membrane specializations

History

Cork Bark by Robert Hooke 1665
  • Robert Hooke (1635-1703) - used early microscopes to view cork tree bark, was the first to use the term CELL
  • Robert Brown 1825 - identified nuclei in plant cells
  • Theodor Schwann (animals) together with Matthias Schleiden (plants) 1839 developed the cell theory

Cell Theory

  1. All organisms consist of one or more cells
  2. The cell is the basic unit of structure for all cells
  3. All cells arise only from preexisting cells
Membrane Research History 
For background information only (not assessable).
  • 1890 Charles Overton - selective permeation of membranes, non-polar pass through (lipid soluble), polar refractory, lipids present as a coat
  • 1905 Irving Langmuir - lipids faced with heads towards water away from organic solvents
  • 1925 Gorter and Grendel - monolayer of lipid isolated from rbc, twice (2x) surface area of cell (bilayer)
  • 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, both hydrophobic and hydrophilic, alternating -phobic and -philic represent trans-membrane loops. glycoprotein carbohydrate groups on outer surface
  • 1997 Simons - cholesterol to form rafts that move within the fluid bilayer (Simons K, Ikonen E. Nature 1997 Jun 5;387(6633):569-72)

Plasma Membrane Images

The cell membrane (plasma membrane or plasmalemma) encloses or covers all cell types and is 7 microns thick (1000 times smaller than the RBC).

Begin by looking at some of the different ways of seeing microscopically membranes.

Membrane - Light Micrograph

CellB35x10L2.jpg Eo104le.jpg

Membrane - Scanning Electron Micrograph

Red White Blood cells.jpg Mycobacterium tuberculosis bacteria.jpg


Membrane - Transmission Electron Micrograph

Plasma and Organelle Membranes CDCcandida.jpg

Compartments

  • Physical Compartments - membrane bound - Nucleus, Cytoplasm, Organelles
    • Cell nomenclature based upon presence or absence of these compartments (eukaryotic, prokaryotic)
  • Functional Compartments - can occur within cytoplasm or membrane bound organelles - spatial localization, targeting, activation and inactivation, signaling
  • Compartments are Dynamic - Movies show flexibility of membranes and their changing shape and size. (Membrane Fluidity)

Links: FRAP | MBC - Membrane Fluidity

Major Cellular Compartments

Proposed model for 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

Nuclear Compartment
  • Nuclear matrix - consisting of Intermediate filaments (lamins)
  • Nucleoli (functional compartment - localised transcription DNA of RNA genes)
  • Chromosomes (DNA and associated proteins)
  • Do not see chromosomes when not dividing (in interphase) only during mitosis and meiosis
Cytoplasmic Compartment
  • Cytoplasmic Organelles - membrane bound structures (endoplasmic reticulum, golgi apparatus, mitochondria, lysosomes, peroxisomes, vesicles)
  • Cytoskeleton - 3 filament systems
  • Cytoplasmic “structures” - Ribosomes (DNA -> mRNA -> Protein), Proteins, Receptors, signaling, metabolism, structural and Viruses, bacteria, prions
  • Functional compartments - occur in nucleus, cytoplasm, in organelles and outside organelles
    • signaling, metabolic reactions, processing genetic information, cytoskeleton dynamics, vesicle dynamics

Membrane Functions

Cell (Plasma) and Organelle Membranes (electron microscope image)
  • Form compartments
  • Allow “specialization”
  • Metabolic and biochemical
  • Localization of function
  • Regulation of transport
  • Detection of signals
  • Cell-cell communication
  • Cell Identity

Membrane Components

Model of Cell (plasma) membrane structure
  • first compartment formed
  • prokaryotes (bacteria) just this 1 compartment
  • eukaryotic cells many different compartments
  • Contains - phospholipids, proteins and cholesterol

Membrane model 02.jpg

Membrane Size

Phospholipids

Membranes contain phospholipids, glycolipids, and steroids.


  • Main lipid components include: phosphatidylcholine (~50%), phosphatidylethanolamine (~10%), phosphatidylserine (~15%), sphingolipids (~10%), cholesterol (~10%) and phosphatidylinositol (1%).
  • 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: Three views of a cell membrane | Figure 2-22. Phospholipid structure and the orientation of phospholipids in membranes


Phospholipid Orientation

Phospholipid Orientation


Lipid rafts

Membrane Proteins

  • Proteins can be embedded in the inner phospholipid layer, outer phospholipid layer or span both layers (20-30% of the genome encodes membrane proteins PMID 9568909) Some proteins are folded such that they span the membrane in a series of “loops”
  • Some membrane protein functions: transport channels, enzyme reactions, cytoskeleton link, cell adhesion and cell identity


Links: Figure 17-21. Topologies of some integral membrane proteins synthesized on the rough ER

Membrane Receptors - Insulin, glucagon and glucose transporter.


Membrane Insulin Receptors

The insulin receptor is embedded in the cell plasma membrane.
  1. Elevated blood glucose stimulate release of insulin
  2. Insulin acts on cells thoughout the body to stimulate uptake, utilization and storage of glucose.
  3. Effects of insulin on glucose metabolism vary depending on the target tissue.
Insulin glucose metabolism.jpg

Insulin glucose metabolism


Muscle, adipose and other tissues. Liver
  • Insulin facilitates entry of glucose.
  • Insulin allows uptake of glucose (by GLUT4 transporter) being made available on the plasma membrane.
  • Insulin stimulates storage of glucose as glycogen.
Links: Physiologic Effects of Insulin

Membrane Glycoproteins

  • Glycoproteins are proteins which have carbohydrate groups (sugars) attached
  • to produce these proteins go through a very specific cellular pathway of organelles (secretory pathway)
  • to 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)

Membrane Cholesterol

Model of Cell (plasma) membrane structure
  • Small molecule embedded between the phospholipid molecules and regulates lipid mobility (MH - see rafts)
  • Cholesterol can be at different concentrations in different regions of plasma membrane distribution
  • Functions: control membrane protein activity and "raft” formation, fine tuning of membrane lipid composition, organization/dynamics, function

Links: MBoC Figure 10-9. Cholesterol in a lipid bilayer

Bacterial Membranes

  • Bacteria with double membranes (Example: E. coli)
    • inner membrane is the cell's plasma membrane
    • Gram Negative do not retain dark blue dye used in gram staining
  • Bacteria with single membranes (Example: staphylo-cocci and streptococci)
    • thicker cell walls
    • Gram Positive because they do retain blue dye
    • single membrane comparable to inner (plasma) membrane of gram negative bacteria

Specializations

Desmosome

Cell adhesion summary.png

Cell potassium channels

Adhesion - junctions allow cells to attach to each other and the non-cellular material that they are embedded within (extracellular matrix)

  • There are several different types that span the membrane and link to the cell skeleton.
  • Adhesion types: Desmosomes ( = macula adherens), Adherens Junctions ( = zonula adherens), Septate Junctions, Tight Junctions, Gap Junctions
  • Cells will have some or all of these junction types

Membrane 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 - Membrane phospholipid impermeable to ions, protein channels permit rapid ion flux

  • 75 + different ion channels, opening/closing, “gating” of ions
    • 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

Cell Death - most cells die by a programmed cell death (Apoptosis)

  • membrane "blebbing" encloses cellular component fragments - prevents "leaking" material into tissues

Membrane Transport Disease - Cystic Fibrosis 1989 Collins (US), Tsui and Riordan (Canada) - Chloride channel protein mutation, point mutant, folded improperly, trapped and degraded in ER

Links: Time-lapse movie of human HeLa cells undergoing apoptosis PMID: 18073771 | Example of early apoptotic blebbing PMID:16129889

References

Science Lectures: Cell Membranes and Compartments | Cell Nucleus | Cell Mitochondria

Molecular Cell Biology 4th ed., Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E., New York: W. H. Freeman & Co., 1999. The Cell- A Molecular Approach Movies

vesicle dynamics

Videos

Membrane
Flexibility
Membrane
Specialisations (cilia)
Moving
Compartments
Changing
Compartments (ER)
Cells.jpg
 ‎‎Chemotaxis
Page | Play
Microtubule movie 1.jpg
 ‎‎Microtubules
Page | Play
Microtubule movie 2.jpg
 ‎‎Microtubules
Page | Play
Endoplasmic reticulum movie 1.jpg
 ‎‎Endoplasmic Reticulum
Page | Play


Here are some general introductory videos to help understand concepts of cell membranes and compartments.

A general introduction to cell membranes.


Cell Compartments


Active and Passive Transport


Having difficulty with these concepts? Here is a very simplified (high school level) description of cell structure.

Membrane Terms

  • adhesion junction - membrane specialization allowing either cell-cell or cell-extracellular matrix adhesion generally in multicellular organisms.
  • bilayer - having two layers, refers to the 2 lipid layers of a single membrane.
  • blebbing - a plasma membrane change often associated with apoptosis. The underlying cell cytoskeleton is disrupted leading to a the bubbling of the plasma membrane, which will enclose cytoplasmic and nuclear components.
  • cholesterol - small steroid metabolite that decreases membrane motility involved in many membrane functions (endocytosis, membrane rafts). Bacterial membranes (except for Mycoplasma and some methylotrophic bacteria) have no sterols, they lack the enzymes required for sterol biosynthesis.
  • electron microscopy - a microscope technique that uses beams of electrons instead of light to generate high resolution images of cellular components. This technique historically gave the first images of the membrane bilayer structure.
  • functional compartment - a specialized region formed within a cell which is not limited by a membrane, compared to a "structural compartment".
  • glucagon receptor - G-protein coupled type receptor found in plasma membrane activated by glucagon. Activation increases blood glucose levels, opposite of insulin.
  • glucose transporter - GLUT4 is the insulin-regulated glucose transporter found in plasma membrane in adipose tissues and skeletal and cardiac muscle responsible for insulin-regulated glucose transport into the cell.
  • Gram negative - term used to describe bacteria which do not retain the Gram dye when stained. These are bacteria with double membranes, the inner membrane is the cell's plasma membrane (Example: E. coli).
  • Gram positive - term used to describe bacteria which do retain the Gram dye when stained. These are bacteria with single membranes and thicker cell wall (Example: staphylo-cocci and streptococci).
  • insulin receptor - tyrosine kinase type receptor found in plasma membrane activated by insulin, IGF-I, IGF-II. Activation has many effects including increasing expression of high affinity glucose transporter (Glut4).
  • lipids - basic molecules forming the lipid bilayer as phospholipids, glycolipids, and steroids. The main lipid components include phosphatidylcholine (~50%), phosphatidylethanolamine (~10%), phosphatidylserine (~15%), sphingolipids (~10%), cholesterol (~10%), and phosphatidylinositol (1%). Medical Microbiology - Plasma (Cytoplasmic) Membranes
  • liposome - (lipid vesicle) is a small aqueous compartment surrounded by a lipid bilayer.
  • membrane cytoskeleton the components of the cell cytoskeleton that directly underly either the cell (plasma) and nuclear membranes.
  • micelle - is a small compartment surrounded by a single lipid layer.
  • phospholipid - the basic molecule forming the lipid bilayer of a typical membrane (see also lipid).
  • raft - (lipid rafts, membrane raft) term used to describe stabilized regions that form within membranes. These rafts "float" within the lipid membrane and are formed by cholesterol altering (stabilizing) the fluidity of the local membrane.
  • receptor - usually protein most often found on the surface of a cell (plasma membrane) that receives signals originating externally from the cell.
  • structural compartment - a specialized region formed within a cell which is limited by a membrane, compared to a "functional compartment".
  • vesicle - general term given to any membrane enclosing material within the cytoplasm.
  • protein-to-lipid ratio the analysis of membranes by separating the 2 main components. For example, bacterial plasma membranes are approximately 3:1, close to those for mitochondrial membranes.

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G