[Expand] Pre-Medicine Links Biology 1 - Cell Types | Biology 2 - Cell Compartments, Membranes | Biology 3-4 - Cell Export/Import | Biology 5 - Cell Cycle | Biology 7 - Cell Filament Systems | Biology 8 - Embryology (https://php.med.unsw.edu.au/embryology/index.php?title=Pre-Medicine_Program_-_Embryology) | 2016 Note - These are the 2015 lecture links and some content provided/replaced by other lecturers for 2016. Dr Mark Hill Eukaryotic Cell Physical Compartments Pre-Medicine Program - Cell Compartments and Membranes From CellBiology Cell Membranes and Compartments About Today's Class Helpful Hints You will also have a summary of today's class in your course handout. Clicking on the images, and opening them, will show more information about the topic. For example Eukaryotic Cell Physical Compartments Pre-Med specific information with the images is in a collapsible table (expand them for your class information) Pre-Medicine Program - Membranes and Compartments Introduction 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.
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Pre-Medicine LinksBiology 1 - Cell Types | Biology 2 - Cell Compartments, Membranes | Biology 3-4 - Cell Export/Import | Biology 5 -Cell Cycle | Biology 7 - Cell Filament Systems | Biology 8 - Embryology(https://php.med.unsw.edu.au/embryology/index.php?title=Pre-Medicine_Program_-_Embryology) | 2016 Note - Theseare the 2015 lecture links and some content provided/replaced by other lecturers for 2016.
Dr Mark Hill
Eukaryotic Cell Physical Compartments
Pre-Medicine Program - Cell Compartments andMembranesFrom CellBiology
Cell Membranes and CompartmentsAbout Today's Class
Helpful Hints
You will also have a summary of today's class in your course handout.Clicking on the images, and opening them, will show more information about the topic.
For example Eukaryotic Cell Physical Compartments
Pre-Med specific information with the images is in a collapsible table (expand them for yourclass information)
Pre-Medicine Program - Membranes and Compartments
IntroductionA major difference between eukayotes and prokaryotes is thepresence of physical compartments (membrane bound) withinthe cell. These compartments allow the separation/specializationof processes within the cell. There also exist within each of thesephysical compartments, functional compartments where specificprocesses may occur or are restricted too. This lecture is anintroduction to compartments within the cell and membranes.The key components are: cell compartments, membranestructure, membrane models, membrane specializations.
Medications act on cells or tissues and can mimic, blockor activate metabolic or signalling pathways.Membranes form compartments and are involved insignalling
Insulin, glucagon, hormone and neurotransmitterreceptors 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.
ObjectivesUnderstand the concept of separate intracellular spacesUnderstand the structure of membranesUnderstand the difference between physical and functional compartmentsBrief understanding of membrane specializations
HistoryRobert Hooke (1635-1703) - used early microscopes to view cork tree bark, wasthe first to use the term CELLRobert Brown 1825 - identified nuclei in plant cellsTheodor Schwann (animals) together with Matthias Schleiden (plants) 1839developed the cell theory
Cell Theory
1. All organisms consist of one or more cells2. The cell is the basic unit of structure for all cells3. All cells arise only from preexisting cells
Membrane Research History
Plasma Membrane ImagesThe cell membrane (plasma membrane or plasmalemma) encloses or covers all celltypes and is 7 microns thick (1000 times smaller than the RBC).
Begin by looking at some of the different ways of seeing microscopically membranes.
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. (MembraneFluidity)
Links: FRAP (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=FRAP&rid=mcb.figgrp.1162) | MBC - MembraneFluidity (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=Membrane%20Proteins&rid=mcb.figgrp.1161)
Major Cellular CompartmentsNucleus (nuclear) - contains a single organelle compartmentCytoplasm (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 (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=hepatocyte&rid=mboc4.figgrp.4123)
Table 12-1. Relative Volumes Occupied by the Major Intracellular Compartments in a Liver Cell (Hepatocyte)(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=hepatocyte&rid=mboc4.table.2135) | Table 12-2. Relative Amountsof Membrane Types in Two Kinds of Eucaryotic Cells (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?
Cell (Plasma) and Organelle Membranes (electronmicroscope image)
highlight=hepatocyte&rid=mboc4.table.2136)
Nuclear Compartment
Nuclear matrix -consisting of Intermediatefilaments (lamins)Nucleoli (functionalcompartment - localisedtranscription DNA ofRNA genes)Chromosomes (DNA andassociated proteins)Do not see chromosomeswhen not dividing (ininterphase) only duringmitosis and meiosis
Cytoplasmic Compartment
Cytoplasmic Organelles - membrane boundstructures (endoplasmic reticulum, golgiapparatus, mitochondria, lysosomes,peroxisomes, vesicles)Cytoskeleton - 3 filament systemsCytoplasmic “structures” - Ribosomes (DNA -> mRNA -> Protein), Proteins, Receptors,signaling, metabolism, structural and Viruses,bacteria, prionsFunctional compartments - occur in nucleus,cytoplasm, in organelles and outsideorganelles
Membrane FunctionsForm compartmentsAllow “specialization”Metabolic and biochemicalLocalization of functionRegulation of transportDetection of signalsCell-cell communicationCell Identity
prokaryotes (bacteria) just this 1 compartmenteukaryotic cells many different compartmentsContains - phospholipids, proteins and cholesterol
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 lipidbilayer.A micelle is a small compartment surrounded by a single lipid layer.
Links: Three views of a cell membrane (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.figgrp.1862) | Figure 2-22. Phospholipid structure and theorientation of phospholipids in membranes(http://www.ncbi.nlm.nih.gov/books/NBK26883/figure/A211/) Phospholipid Orientation
Membrane ProteinsProteins can be embedded in the innerphospholipid layer, outer phospholipid layer orspan both layers (20-30% of the genome encodesmembrane proteins PMID 9568909) Someproteins are folded such that they span themembrane in a series of “loops”Some membrane protein functions: transportchannels, enzyme reactions, cytoskeleton link, celladhesion and cell identity
Links: Figure 17-21. Topologies of some integral membrane proteins synthesized on the rough ER(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=Transport,Membrane&rid=mcb.figgrp.4776)
Membrane Receptors - Insulin, glucagon and glucose transporter.
The insulin receptor is embedded in the cell plasma membrane.
1. Elevated blood glucose stimulate release of insulin2. 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
Muscle, adipose and other tissues. Liver
Insulin facilitates entry of glucose.Insulin allows uptake of glucose (by GLUT4 transporter) being madeavailable on the plasma membrane.
Insulin stimulates storage ofglucose as glycogen.
Links: Physiologic Effects of Insulin(http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html)
Membrane GlycoproteinsGlycoproteins are proteins which have carbohydrate groups (sugars) attachedto 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 CholesterolSmall molecule embedded between the phospholipid molecules and regulateslipid mobility (MH - see rafts)Cholesterol can be at different concentrations in different regions of plasmamembrane distributionFunctions: control membrane protein activity and "raft” formation, fine tuning ofmembrane lipid composition, organization/dynamics, function
Links: MBoC Figure 10-9. Cholesterol in a lipid bilayer(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=cholesterol&rid=cell.figgrp.2458)
Bacterial MembranesBacteria with double membranes (Example: E. coli)
inner membrane is the cell's plasma membraneGram Negative do not retain dark blue dye used in gram staining
Bacteria with single membranes (Example: staphylo-cocci and streptococci)thicker cell wallsGram Positive because they do retain blue dyesingle membrane comparable to inner (plasma) membrane of gram negative bacteria
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 JunctionsCells will have some or all of these junction types
Membrane Transport - Three major forms of transport across the membrane
Passive - Simple diffusionFacilitated - transport proteinsActive - 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 ionsVoltage-gated - propogation of electrical signals along nerve, muscle
Ligand-gated - opened by non-covalent, reversible bindingof ligand between nerve cells, nerve-muscle, gland cellsMechanical-gated - regulated by mechanical deformationGap junction - allow ions to flow between adjacent cellsopen/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, pointmutant, folded improperly, trapped and degraded in ER
Links: Time-lapse movie of human HeLa cells undergoingapoptosis(http://www.nature.com/nrm/journal/v9/n3/extref/nrm2312-s1.mov) PMID: 18073771(http://www.ncbi.nlm.nih.gov/pubmed/18073771?) | Example ofearly apoptotic blebbing(http://jcs.biologists.org/content/vol118/issue17/images/data/4059/DC1/JCS14488Video1.mov) PMID:16129889(http://www.ncbi.nlm.nih.gov/pubmed/16129889?)
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
Having difficulty with these concepts? Here is a very simplified (high school level) description of cell structure.
Biology: Cell Structure
Membrane Termsadhesion junction - membrane specialization allowing either cell-cell or cell-extracellular matrix adhesion generallyin 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 disruptedleading 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) haveno 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 resolutionimages 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, comparedto a "structural compartment".glucagon receptor - G-protein coupled type receptor found in plasma membrane activated by glucagon. Activationincreases blood glucose levels, opposite of insulin.
glucose transporter - GLUT4 is the insulin-regulated glucose transporter found in plasma membrane in adiposetissues 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 bacteriawith 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 withsingle 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 lipidcomponents include phosphatidylcholine (~50%), phosphatidylethanolamine (~10%), phosphatidylserine (~15%),sphingolipids (~10%), cholesterol (~10%), and phosphatidylinositol (1%). Medical Microbiology - Plasma(Cytoplasmic) Membranes (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=plasma%20membrane&rid=mmed.section.305#306)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) andnuclear 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 localmembrane.receptor - usually protein most often found on the surface of a cell (plasma membrane) that receives signalsoriginating 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 plasmamembranes are approximately 3:1, close to those for mitochondrial membranes.
Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G
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