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Pre-Medicine Program - CellCompartments and MembranesCell Membranes and Compartments

About Today's Class

Lecture Slides 2016

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You will also have a summary of today's class in your course handout.Clicking on the images, and opening them, will show moreinformation about the topic.

For example Eukaryotic Cell Physical Compartments

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Pre-Medicine Program - Membranes and Compartments

Introduction

Eukaryotic Cell Physical Compartments

A major difference between eukayotes and prokaryotes is the presence of

physical compartments (membrane bound) within the cell. Thesecompartments allow the separation/specialization of processes within thecell. There also exist within each of these physical compartments,functional compartments where specific processes may occur or arerestricted too. This lecture is an introduction to compartments within thecell 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 activatemetabolic or signalling pathways.Membranes form compartments and are involved in signalling

Insulin, glucagon, hormone and neurotransmitter receptors areembedded in the plasma membrane.

Nutrients - Cells transport nutrients across cell membranes intospecific compartments for use.

Glucose transporter embedded in the plasma membrane.Waste - Cells transport waste across cell membranes into extracellularspecific compartments for excretion.

Objectives

Understand the concept of separate intracellular spacesUnderstand the structure of membranesUnderstand the difference between physical and functionalcompartmentsBrief understanding of membrane specializations

History

Robert Hooke (1635-1703) - used early microscopes to view cork treebark, was the first to use the term CELLRobert Brown 1825 - identified nuclei in plant cellsTheodor Schwann (animals) together with Matthias Schleiden(plants) 1839 developed the cell theory

Cell Theory

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Cork Bark by Robert Hooke1665

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 Images

The cell membrane (plasma membrane orplasmalemma) encloses or covers all cell typesand is 7 microns thick (1000 times smaller thanthe RBC).

Begin by looking at some of the different ways of seeing microscopicallymembranes.

Membrane - Light Micrograph

Membrane - Scanning Electron Micrograph

Membrane - Transmission Electron Micrograph

Compartments

Physical Compartments - membrane bound - Nucleus, Cytoplasm,Organelles

Cell nomenclature based upon presence or absence of thesecompartments (eukaryotic, prokaryotic)

Functional Compartments - can occur within cytoplasm ormembrane bound organelles - spatial localization, targeting,activation and inactivation, signaling

Compartments are Dynamic - Movies show flexibility ofmembranes and their changing shape and size. (Membrane Fluidity)

Links: FRAP | MBC - Membrane Fluidity

Major Cellular Compartments

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 IntracellularCompartments in a Liver Cell (Hepatocyte) | Table 12-2. Relative Amountsof Membrane Types in Two Kinds of Eucaryotic Cells

Nuclear Compartment

Nuclear matrix -consisting ofIntermediate filaments(lamins)Nucleoli (functionalcompartment - localisedtranscription DNA ofRNA genes)Chromosomes (DNAand associated proteins)Do not seechromosomes when notdividing (in interphase)only during mitosis andmeiosis

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 innucleus, cytoplasm, in organelles andoutside organelles

signaling, metabolic reactions,processing genetic information,cytoskeleton dynamics, vesicledynamics

Membrane Functions

Form compartmentsAllow “specialization”Metabolic and biochemicalLocalization of functionRegulation of transportDetection of signals

Cell (Plasma) and Organelle Membranes(electron microscope image)

Cell-cell communicationCell Identity

Membrane Components

first compartment formedprokaryotes (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 compartmentsurrounded by a lipid bilayer.A micelle is a small compartment surrounded by a singlelipid layer.

Links: Three views of a cell membrane | Figure 2-22.Phospholipid structure and the orientation of phospholipids inmembranes

PhospholipidOrientation

Membrane Proteins

Proteins can be embedded in the inner phospholipid layer, outerphospholipid layer or span both layers (20-30% of the genomeencodes membrane proteins PMID 9568909) Some proteins arefolded such that they span the membrane in a series of “loops”Some membrane protein functions: transport channels, enzymereactions, cytoskeleton link, cell adhesion and cell identity

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

Membrane Receptors - Insulin, glucagon and glucose transporter.

Membrane Insulin Receptors

The insulin receptor is embedded in the cell plasmamembrane.

1. Elevated blood glucose stimulate release of insulin

2. Insulin acts on cells thoughout the body tostimulate uptake, utilization and storage of glucose.

3. Effects of insulin on glucose metabolism varydepending on the target tissue.

Insulin glucosemetabolism

Muscle, adipose and other tissues. Liver

Insulin facilitates entry of glucose.Insulin allows uptake of glucose (by GLUT4transporter) being made available on theplasma membrane.

Insulin stimulatesstorage of glucoseas glycogen.

Links: Physiologic Effects of Insulin

Membrane Glycoproteins

Glycoproteins are proteins which have carbohydrate groups (sugars)attachedto produce these proteins go through a very specific cellular pathwayof organelles (secretory pathway)to reach the cell surface where they are either secreted (form part ofthe extracellular matrix)or are embedded in the membrane with the carbohydrate grouped onthe outside surface (integral membrane protein)

Membrane Cholesterol

Small molecule embedded between the phospholipid molecules andregulates lipid mobility (MH - see rafts)Cholesterol can be at different concentrations in different regions ofplasma membrane distributionFunctions: 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 membraneGram Negative do not retain dark blue dye used in gram staining

Bacteria with single membranes (Example: staphylo-cocci andstreptococci)

thicker cell wallsGram Positive because they do retain blue dyesingle membrane comparable to inner (plasma) membrane ofgram negative bacteria

Specializations

Adhesion - junctions allow cells toattach to each other and the non-cellular material that they areembedded within (extracellularmatrix)

There are several differenttypes that span the membraneand link to the cell skeleton.Adhesion types: Desmosomes (= macula adherens), AdherensJunctions ( = 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 themembrane

Passive - Simple diffusionFacilitated - transport proteinsActive - transport proteins for nutrient uptake, secretion, ion balance

Ion Channels - Membrane phospholipid impermeable to ions, proteinchannels permit rapid ion flux

75 + different ion channels, opening/closing, “gating” of ionsVoltage-gated - propogation of electrical signals along nerve,muscleLigand-gated - opened by non-covalent, reversible binding ofligand 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), Tsuiand Riordan (Canada) - Chloride channel protein mutation, point mutant,folded improperly, trapped and degraded in ER

Links: Time-lapse movie of human HeLa cells undergoing apoptosisPMID: 18073771 | Example of early apoptotic blebbingPMID:16129889

References

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

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

vesicle dynamics

Videos

Here are some general introductory videos to help understand concepts ofcell 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 (highschool level) description of cell structure.

Membrane Terms

adhesion junction - membrane specialization allowing either cell-cell or cell-extracellular matrix adhesion generally in multicellularorganisms.bilayer - having two layers, refers to the 2 lipid layers of a singlemembrane.blebbing - a plasma membrane change often associated withapoptosis. The underlying cell cytoskeleton is disrupted leading to athe bubbling of the plasma membrane, which will enclose cytoplasmicand nuclear components.cholesterol - small steroid metabolite that decreases membranemotility involved in many membrane functions (endocytosis,membrane rafts). Bacterial membranes (except for Mycoplasma andsome methylotrophic bacteria) have no sterols, they lack the enzymesrequired for sterol biosynthesis.electron microscopy - a microscope technique that uses beams ofelectrons instead of light to generate high resolution images of cellular

components. This technique historically gave the first images of themembrane bilayer structure.functional compartment - a specialized region formed within acell which is not limited by a membrane, compared to a "structuralcompartment".glucagon receptor - G-protein coupled type receptor found inplasma membrane activated by glucagon. Activation increases bloodglucose levels, opposite of insulin.glucose transporter - GLUT4 is the insulin-regulated glucosetransporter found in plasma membrane in adipose tissues and skeletaland cardiac muscle responsible for insulin-regulated glucose transportinto the cell.Gram negative - term used to describe bacteria which do not retainthe Gram dye when stained. These are bacteria with doublemembranes, the inner membrane is the cell's plasma membrane(Example: E. coli).Gram positive - term used to describe bacteria which do retain theGram dye when stained. These are bacteria with single membranesand thicker cell wall (Example: staphylo-cocci and streptococci).insulin receptor - tyrosine kinase type receptor found in plasmamembrane activated by insulin, IGF-I, IGF-II. Activation has manyeffects including increasing expression of high affinity glucosetransporter (Glut4).lipids - basic molecules forming the lipid bilayer as phospholipids,glycolipids, and steroids. The main lipid components includephosphatidylcholine (~50%), phosphatidylethanolamine (~10%),phosphatidylserine (~15%), sphingolipids (~10%), cholesterol (~10%),and phosphatidylinositol (1%). Medical Microbiology - Plasma(Cytoplasmic) Membranesliposome - (lipid vesicle) is a small aqueous compartmentsurrounded by a lipid bilayer.membrane cytoskeleton the components of the cell cytoskeletonthat 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 atypical membrane (see also lipid).raft - (lipid rafts, membrane raft) term used to describe stabilizedregions that form within membranes. These rafts "float" within thelipid 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 fromthe cell.structural compartment - a specialized region formed within a cellwhich is limited by a membrane, compared to a "functionalcompartment".vesicle - general term given to any membrane enclosing materialwithin the cytoplasm.protein-to-lipid ratio the analysis of membranes by separating the2 main components. For example, bacterial plasma membranes areapproximately 3:1, close to those for mitochondrial membranes.

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider CodeNo. 00098G