11 cell bio membrane structure_post

Chapter 11: Chapter 11: Membrane StructureMembrane Structure

Membrane Structure• The Lipid Bilayer• Membrane Proteins

THE LIPID BILAYERTHE LIPID BILAYER

The Lipid Bilayer• Boundary• 2 sheets lipid bilayer, 5 nm thick• Exhibits ____________ permeability

– Allows some substances to cross it more easily than others

KEY CONCEPT

Evolution to eukaryotic cells allowed...

COMPARTMENTALIZATIONCOMPARTMENTALIZATION

Figure 11-1 Essential Cell Biology (© Garland Science 2010)

IMPORTANCE OF COMPARTMENTALIZATION

• Plasma membranes can carry out unique functions– Ion transport and transport of other molecules– Evolution of receptor molecules

IMPORTANCE OF COMPARTMENTALIZATION

• Cells can be larger since _________ is not an issue

Figure 11-3 Essential Cell Biology (© Garland Science 2010)

Membrane Functions• IMPORT nutrients FROM environment• EXPORT waste TO environment• Maintain concentration GRADIENTS• Cell-cell communication• Capacity for movement

Functions based on membrane composition...

Membrane Phospholipid

________________

The presence of hydrophobichydrophobic

ANDhydrophilichydrophilic

regions gives unique functionality

–

+ +H2O

““charged”charged”polarpolar

hydrophilichydrophilic

Refresher on Water Characteristics

Figure 11-8 Essential Cell Biology (© Garland Science 2010)

Figure 11-9 Essential Cell Biology (© Garland Science 2010)

Phospholipid Head Group

1) Glycerol2) Phosphate3) Functional Group

– Choline– Ethanolamine– Serine– Inositol

Most Popular Phospholipid....Phosphatidyl Choline

KEY CONCEPTDue to their dual amphipathic nature...

Phospholipids form...__________________

andsealed compartments in watersealed compartments in water

(The most energetically favorable ‘conformation’)

Fig 11-11Fig 11-11

Lipid Bilayer

Water molecules “_______” hydrophobic molecules

Think about it...

Why do “compartments” form?

Every molecule is “HAPPY”...

Think about it...

What would happen if phospholipids were added to this apparatus?

(Note: There are not enough phospholipids to form a 25nm sphere.)

Figure 11-14 Essential Cell Biology (© Garland Science 2010)

KEY CONCEPT

The lipid bilayer is _________

Lipids are moving within each layer and spinning

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)

The Fluidity of Phospholipids• Rotation

– common

• Flexible

KEY CONCEPT

The fluidity of a lipid bilayer depends on its composition

Factors Effecting the Fluidity of Membranes

• More fluid more movement within membrane• Factors effecting fluidity:

– Temperature– Fatty acid tails– Cholesterol content

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

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:

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)

Cholesterol contentCholesterol content• High cholesterol rigid• Low cholesterol less rigid

The Fluidity of Membranes

Cholesterol

Figure 11-16 Essential Cell Biology (© Garland Science 2010)

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

KEY CONCEPT

FLUIDITY is ESSENTIAL:

Membrane function Movement of membrane proteins

http://www.youtube.com/watch?v=ULR79TiUj80

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

Fig 11-17

Membranes are Asymmetrical...

• Different molecules are found on different sides of the layers

Fig 11-17

Asymmetry Initiated in ER

ER

Golgiapparatus

Vesicle

Plasma membrane

Proteins

ProteinsLipids

Carbohydrates

Membrane ‘Trafficking’Fusing of the Vesicles

Membrane ‘Trafficking’Membrane Phospholipid Synthesis

• Enzymes attached to organelles make phospholipids– Cytosolic layer– Use fatty acids in cytoplasm as substrates

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

Membrane ‘Trafficking’_____________• Transfer phospholipids...

– FROM cytosolic side TO non-cytosolic face• Keeps the growth of each layer the same

KEY CONCEPT

Membranes are permeable

Membrane Permeability• The membrane serves

as a barrier to molecules that are:– Hydrophilic– Charged

• SIZE also affects the relative permeability!

So if phospholipids won’t let in important molecules...

How DO those molecules enter the cell??

MEMBRANE PROTEINSMEMBRANE PROTEINS

Fluid Mosaic Model• Mosaic of phospholipids and proteins

KEY CONCEPT

Membrane function depends on membrane proteins

Figure 11-20 Essential Cell Biology (© Garland Science 2010)

Common Functions of Membrane Proteins

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...

KEY CONCEPT

Proteins associate with membranes in Proteins associate with membranes in various waysvarious ways

• _________ proteins are bound to the surface of the membrane

Types of Membrane Proteins

• ______ proteins______ proteins penetrate the hydrophobic core • Transmembrane proteins Transmembrane proteins span the membrane

Types of Membrane Proteins

Integralprotein

TransmembraneIntegralprotein

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?

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

integral peripheral

Integral “disrupted by detergents”

KEY CONCEPT

A polypeptide usually crosses the A polypeptide usually crosses the membrane as an membrane as an __________________

Review of Protein Components...• Amino acid

– Amino group Basic– Carboxyl group Acidic

• Functional groups determine “properties”

Secondary Structure

β pleated sheet

Examples ofamino acidsubunits

α helix

Review of Protein Components

The Alpha-Helix

• Nonpolar groups interact with hydrophobic core

• Orientation of a membrane protein cannot change

KEY CONCEPT

Numerous alpha-helices can create an Numerous alpha-helices can create an aqueous poreaqueous pore

Fig 11-25

The Alpha-Helix

N-terminus

C-terminus

Helix

CYTOPLASMICSIDE

EXTRACELLULARSIDE

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?

KEY CONCEPT

Numerous ß-strands can create a larger pore: ß-barrel

The Beta-Barrel

Alpha-Helix vs. Beta-Barrel Channels

• Barrels are bigger

Think about it...

• Why do transmembrane proteins REMAIN in the membrane?

Note:Membrane Proteins Are

Difficult to Study…They are generally INSOLUBLE and UNSTABLE in aqueous environment.

KEY CONCEPT

Detergents can be used to help researchers study membrane proteins.

DETERGENTSDETERGENTSsolubilize the membrane

Detergents

• Small• Amphipathic • Lipid-like• Single hydrophobic tail

Micelles• Aggregates of detergent molecules

Mixing Detergents and Membranes• Hydrophobic ends bind to hydrophobic region of

membrane components• Hydrophilic heads act as “SHIELDS”

Protein Analysis• Proteins can be separated by size

– Polyacrylamide-gel electrophoresis

Detergents are great, but...

Complete structure of many membrane proteins are unknown because....

X-ray Crystallography• Crystallize protein X-rays diffraction

patternDiffractedX-rays

X-raysource X-ray

beam

Crystal Digital detector X-ray diffractionpattern

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 __________

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

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

Think about it….

• If proteins couldn’t move along the plasma membrane then what would have been the results of that experiment?

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

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?

Now we know plasma membranes are a mosaic of phospholipids and

proteins....

How does the membrane maintain its shape?

KEY CONCEPT

A meshwork of proteins are attached to specialized membrane proteins:

Cell Cortex

(Gives cell rigidity and shape)

Cell Cortex• Acts as a support system

Example: Red Blood Cell• Flattened shape• Cortex made of spectrin

Figure 11-31 Essential Cell Biology (© Garland Science 2010)

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

KEY CONCEPT

Cell surface is coated with carbohydrates

Carbohydrate Terminology• Glycoprotein

– Protein + carbohydrate

Carbohydrate Terminology• Proteoglycan

– Protein + LOTS of carbohydrates

Carbohydrate Terminology• Glycolipid

– Lipid + carbohydrate

Importance of Glycosylation

• Protect surface– Carbohydrates bind to water– “Slimy” surface

• Self-recognition• Protein function• Diversity of “labeling” is unlimited.• Cell-cell recognition

Fig 11-33

Importance of “Sliminess”

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…

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

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.

Chapter 11 DONE...

Any questions??