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Chapter 11: Chapter 11: Membrane StructureMembrane Structure
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Membrane Structure• The Lipid Bilayer• Membrane Proteins
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THE LIPID BILAYERTHE LIPID BILAYER
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The Lipid Bilayer• Boundary• 2 sheets lipid bilayer, 5 nm thick• Exhibits ____________ permeability
– Allows some substances to cross it more easily than others
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KEY CONCEPT
Evolution to eukaryotic cells allowed...
COMPARTMENTALIZATIONCOMPARTMENTALIZATION
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Figure 11-1 Essential Cell Biology (© Garland Science 2010)
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IMPORTANCE OF COMPARTMENTALIZATION
• Plasma membranes can carry out unique functions– Ion transport and transport of other molecules– Evolution of receptor molecules
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IMPORTANCE OF COMPARTMENTALIZATION
• Cells can be larger since _________ is not an issue
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Figure 11-3 Essential Cell Biology (© Garland Science 2010)
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Membrane Functions• IMPORT nutrients FROM environment• EXPORT waste TO environment• Maintain concentration GRADIENTS• Cell-cell communication• Capacity for movement
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Functions based on membrane composition...
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Membrane Phospholipid
________________
The presence of hydrophobichydrophobic
ANDhydrophilichydrophilic
regions gives unique functionality
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–
+ +H2O
““charged”charged”polarpolar
hydrophilichydrophilic
Refresher on Water Characteristics
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Figure 11-8 Essential Cell Biology (© Garland Science 2010)
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Figure 11-9 Essential Cell Biology (© Garland Science 2010)
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Phospholipid Head Group
1) Glycerol2) Phosphate3) Functional Group
– Choline– Ethanolamine– Serine– Inositol
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Most Popular Phospholipid....Phosphatidyl Choline
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KEY CONCEPTDue to their dual amphipathic nature...
Phospholipids form...__________________
andsealed compartments in watersealed compartments in water
(The most energetically favorable ‘conformation’)
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Fig 11-11Fig 11-11
Lipid Bilayer
Water molecules “_______” hydrophobic molecules
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Think about it...
Why do “compartments” form?
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Every molecule is “HAPPY”...
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Think about it...
What would happen if phospholipids were added to this apparatus?
(Note: There are not enough phospholipids to form a 25nm sphere.)
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Figure 11-14 Essential Cell Biology (© Garland Science 2010)
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KEY CONCEPT
The lipid bilayer is _________
Lipids are moving within each layer and spinning
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The Fluidity of Phospholipids• Lateral Diffusion
– 10,000,000 times per second
• “Flip-Flop”– rare
Lateral movement(107 times per second)
Flip-flop( once per month)
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The Fluidity of Phospholipids• Rotation
– common
• Flexible
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KEY CONCEPT
The fluidity of a lipid bilayer depends on its composition
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Factors Effecting the Fluidity of Membranes
• More fluid more movement within membrane• Factors effecting fluidity:
– Temperature– Fatty acid tails– Cholesterol content
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Factors Effecting the Fluidity of Membranes
TEMPERATURETEMPERATURE• As temperatures cools…
– Membranes switch from a fluidfluid to a solidsolid
– Membranes must be fluid to work properly• Usually about as fluid as salad oil
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Factors Effecting the Fluidity of Membranes
Fatty Acid Tails: Unsaturated or Saturated Fatty Acid Tails: Unsaturated or Saturated • Wait a minute...
• What’s the difference between saturated and unsaturated fatty acids?
– Saturated:
– Unsaturated:
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Factors Effecting the Fluidity of Membranes
Fluid
Unsaturated hydrocarbontails with kinks
Viscous
Saturated hydro-carbon tails
Fatty Acid TailsFatty Acid Tails • Unsaturated fatty acids = more ____________
• Saturated fatty acids = more ____________ (think of molasses)
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Cholesterol contentCholesterol content• High cholesterol rigid• Low cholesterol less rigid
The Fluidity of Membranes
Cholesterol
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Figure 11-16 Essential Cell Biology (© Garland Science 2010)
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CholesterolCholesterol + TemperatureTemperature:• Cholesterol “temperature buffer”
– At warmwarm temperatures: • cholesterol restrains movement of phospholipids
– At coolcool temperatures:• maintains fluidity by preventing tight packing
The Fluidity of Membranes
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KEY CONCEPT
FLUIDITY is ESSENTIAL:
Membrane function Movement of membrane proteins
http://www.youtube.com/watch?v=ULR79TiUj80
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KEY CONCEPT
Membranes are asymmetrical
Asymmetry is generated within cell, when the membranes are built at the ER
New phospholipids are incorporated into the CYTOSOLIC LAYER
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Fig 11-17
Membranes are Asymmetrical...
• Different molecules are found on different sides of the layers
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Fig 11-17
Asymmetry Initiated in ER
ER
Golgiapparatus
Vesicle
Plasma membrane
Proteins
ProteinsLipids
Carbohydrates
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Membrane ‘Trafficking’Fusing of the Vesicles
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Membrane ‘Trafficking’Membrane Phospholipid Synthesis
• Enzymes attached to organelles make phospholipids– Cytosolic layer– Use fatty acids in cytoplasm as substrates
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Copyright ©2009 American Society for Biochemistry and Molecular Biology
Fagone, P. et al. J. Lipid Res. 2009;50:S311-S316
Compartmentalization of phospholipid biosynthetic activities
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Membrane ‘Trafficking’_____________• Transfer phospholipids...
– FROM cytosolic side TO non-cytosolic face• Keeps the growth of each layer the same
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KEY CONCEPT
Membranes are permeable
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Membrane Permeability• The membrane serves
as a barrier to molecules that are:– Hydrophilic– Charged
• SIZE also affects the relative permeability!
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So if phospholipids won’t let in important molecules...
How DO those molecules enter the cell??
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MEMBRANE PROTEINSMEMBRANE PROTEINS
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Fluid Mosaic Model• Mosaic of phospholipids and proteins
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KEY CONCEPT
Membrane function depends on membrane proteins
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Figure 11-20 Essential Cell Biology (© Garland Science 2010)
Common Functions of Membrane Proteins
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Think about it...
A protein that pumps Na+ out of the cell is most likely a...
An integrin—attaches to extracellular matrix—is most likely a...
Hexokinase phoshorylates glucose, it is most likely a...
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KEY CONCEPT
Proteins associate with membranes in Proteins associate with membranes in various waysvarious ways
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• _________ proteins are bound to the surface of the membrane
Types of Membrane Proteins
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• ______ proteins______ proteins penetrate the hydrophobic core • Transmembrane proteins Transmembrane proteins span the membrane
Types of Membrane Proteins
Integralprotein
TransmembraneIntegralprotein
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Think about it...Would a peripheral protein be hydrophobic,
hydrophilic, or both?
What about an integral protein?
What about a transmembrane protein?
Which would you expect to have the largest hydrophobic region?
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Proteins Associate With Membranes In Various Ways
• TransmembraneTransmembrane• Membrane-associatedMembrane-associated• Lipid-linked: Lipid-linked: covalently, outer or inner layer
• Protein-protein interactions: Protein-protein interactions: indirect association through OTHER proteins
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integral peripheral
Integral “disrupted by detergents”
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KEY CONCEPT
A polypeptide usually crosses the A polypeptide usually crosses the membrane as an membrane as an __________________
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Review of Protein Components...• Amino acid
– Amino group Basic– Carboxyl group Acidic
• Functional groups determine “properties”
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Secondary Structure
β pleated sheet
Examples ofamino acidsubunits
α helix
Review of Protein Components
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The Alpha-Helix
• Nonpolar groups interact with hydrophobic core
• Orientation of a membrane protein cannot change
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KEY CONCEPT
Numerous alpha-helices can create an Numerous alpha-helices can create an aqueous poreaqueous pore
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Fig 11-25
The Alpha-Helix
N-terminus
C-terminus
Helix
CYTOPLASMICSIDE
EXTRACELLULARSIDE
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Fig 11-25
Think about it...• What type of functional groups would be associated
with the green amino acids?
• What type of functional groups would be associated with the red amino acids?
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KEY CONCEPT
Numerous ß-strands can create a larger pore: ß-barrel
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The Beta-Barrel
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Alpha-Helix vs. Beta-Barrel Channels
• Barrels are bigger
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Think about it...
• Why do transmembrane proteins REMAIN in the membrane?
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Note:Membrane Proteins Are
Difficult to Study…They are generally INSOLUBLE and UNSTABLE in aqueous environment.
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KEY CONCEPT
Detergents can be used to help researchers study membrane proteins.
DETERGENTSDETERGENTSsolubilize the membrane
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Detergents
• Small• Amphipathic • Lipid-like• Single hydrophobic tail
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Micelles• Aggregates of detergent molecules
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Mixing Detergents and Membranes• Hydrophobic ends bind to hydrophobic region of
membrane components• Hydrophilic heads act as “SHIELDS”
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Protein Analysis• Proteins can be separated by size
– Polyacrylamide-gel electrophoresis
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Detergents are great, but...
Complete structure of many membrane proteins are unknown because....
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X-ray Crystallography• Crystallize protein X-rays diffraction
patternDiffractedX-rays
X-raysource X-ray
beam
Crystal Digital detector X-ray diffractionpattern
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X-ray Crystallography• The procedure:The procedure:
– Purified protein undergoes slow precipitation from an aqueous solution
• Membrane proteins don’t like to __________Membrane proteins don’t like to __________
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KEY CONCEPT
Membrane proteins can move along the Membrane proteins can move along the plasma membrane AND can be restricted to plasma membrane AND can be restricted to
specific regions of a cellspecific regions of a cell
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Frye and Edidin: fused the cells hybrid cell
Experiment to Show the Movement of Proteins
RESULTS
Membrane proteins
Mouse cellHuman cell
Hybrid cell
Mixed proteinsafter 1 hour
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Think about it….
• If proteins couldn’t move along the plasma membrane then what would have been the results of that experiment?
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Proteins can also be bound to specific regions...
Tethered to Tethered to cell cortexcell cortex
Tethered Tethered to ECMto ECM
Tethered to surface of Tethered to surface of another cellanother cell
Diffusion Diffusion barriersbarriers
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BLOOD VESSELSBLOOD VESSELS
Think about it...• Protein A: glucose in, Protein B: glucose out• Why wouldn’t the cell want Protein A on the basal
surface?
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Now we know plasma membranes are a mosaic of phospholipids and
proteins....
How does the membrane maintain its shape?
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KEY CONCEPT
A meshwork of proteins are attached to specialized membrane proteins:
Cell Cortex
(Gives cell rigidity and shape)
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Cell Cortex• Acts as a support system
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Example: Red Blood Cell• Flattened shape• Cortex made of spectrin
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Figure 11-31 Essential Cell Biology (© Garland Science 2010)
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Real Life...Muscular DystrophyMutant protein called: dystrophin
–Reduces the stability of the cell cortex–Leads to the development of:
•Loss of muscle function•Progressive muscle weakness•Wheelchair dependent•Cardiac arrest
–Currently incurable
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KEY CONCEPT
Cell surface is coated with carbohydrates
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Carbohydrate Terminology• Glycoprotein
– Protein + carbohydrate
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Carbohydrate Terminology• Proteoglycan
– Protein + LOTS of carbohydrates
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Carbohydrate Terminology• Glycolipid
– Lipid + carbohydrate
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Importance of Glycosylation
• Protect surface– Carbohydrates bind to water– “Slimy” surface
• Self-recognition• Protein function• Diversity of “labeling” is unlimited.• Cell-cell recognition
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Fig 11-33
Importance of “Sliminess”
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Everyday Life…Blood Types• Blood Types: A+, B+, AB+, O+, A-, B-, AB-, O-• What is the most and least common blood type?
• Carbohydrates on the surface of RBC determine blood type…
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Everyday Life…Rh Factor Incompatibility• Rh protein on RBC = +/-• Woman (Rh -) + Man (Rh +)
– If Baby # 1 is Rh + • During delivery mom's and baby's blood mix• Mom produces antibodies to foreign blood
– If Baby #2 is Rh +• Mom’s Rh antibodies recognize baby’s Rh + RBCs and
ATTACK• Leads to swelling and rupture of the baby's RBCs
baby's RBC count can get dangerously low – Can have mild to serious effects
• Anemia Death
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Rh Immune Globin Shot• Antibodies to the Rh factor• Rh immune globulin antibodies locate any Rh-positive
fetal red blood cells that are present• The antibodies attach to the Rh-positive red blood cells,
masking their presence from the mother's immune system
• Prevents immune system from producing its own Rh antibodies
• Although the Rh immune globulin antibodies destroy fetal red blood cells, not enough are destroyed to harm the fetus.
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Chapter 11 DONE...
Any questions??