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8/12/2019 Lecture 1 - Plasma Membrane I (Lipids and Proteins)
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Biology 331Summer 2014
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Dr. Lars PetersenPart II (July 23end)
Office: BI 442
Tel.: 403-
E-mail: [email protected]
Dr. T. Don NguyenPart I (startJuly 21)
Office: BI 387
Tel.: 403-220-8167
E-mail: [email protected]
E-mail to make appointments
E-mails will be replied within 24 hours (48 hours on
weekends)
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Grade components
Midterm exam (July 21) 35%
Tutorial quizzes 10%
Tutorial term project 20%
Final exam 35%
(sometime between August 15 and 18)
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Terms you are expected to be already
familiar with
You need to know the following in terms of their: composition
function
Ribosome Bacteria /ProkaryoteDNA & deoxyribonucleotides Eukaryote
RNA & ribonucleotides Archaea
Sugar (carbohydrate) Multicellular
Lipid UnicellularEnzyme Transposon
Membrane Promoter
Periodic table of elements Gene = open reading frame (ORF)
Protein & amino acids acid and base chemistry
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10 m
1 m
100 mm
(10 cm)
10 mm(1 cm)
1 mm
Human height
Length ofsome nerveand musclecells
Chickenegg
Frog egg
Paramecium
100 m
Unaide
d
eye
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Plasma Membrane
(membrane lipids and proteins)
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Eukaryote Prokaryote
10-100m
0.1-10m
The plasma membrane is an essential
feature for all cells
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Essential roles of membrane
1) Compartmentalization2) Biochemical scaffold
3) Selective permeabilitybarrier
4) Solute transport5) Signalling
6) Intercellular interaction
7) Energy transduction
8) Flexibility
CO2+RuBP
PGA
2
Acid hydrolases
1
ADP+Pi
ATP
4H+
7
H2O3
6
IP3
Ca2+
5
8
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Membranes role # 1: Compartmentalization
Membranes are barriers between sets ofmolecules such as proteins eg. Outside of cell vs. inside Inside of an organelle
vs. cytoplasm
Provides an environment specialized for thefunction / biochemical reactions that take place
within the compartment
Most prokaryotes lack internal membranes,therefore they do not have internal organelles
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Membranes role # 2: Scaffold for biochemical
activities and cytoskeleton attachment
Membranes can act as surfaces for
biochemical reactions/cellular
processes
Some reactions are more efficient in
membranes than in solution
Membranes interact with the internalcytoskeleton; connects plasma
membrane to cytoskeleton
mb
Attachment
protein
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Membranes role # 3: Selective permeability barrier
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Restricts movement of ions: different
ionic compositions on opposite sides
of the membrane.
Allows gradients to be established
Different concentrations of the same
ion on opposite sides of themembrane can form
eg. Important for nerve and muscle
function and energy
mb
H+
H+
H+H+
H+
H+
H+H+
H+
H+
H+
H+H+
H
+
H+
IN OUT
Membranes role # 3: Selective permeability barrier
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Membranes role # 4: Transporting solutes
Membranes are sites where the movement ofmolecules from one compartment to the other.
eg. Ion channels, transporters
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Signals from one side of membrane elicit a response on the
other side; (eg. response to hormones, growth factors,neurotransmitters)
Membranes role # 5: Response to external signals
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Membranes role # 6: Intercellular interactions
Sites where neighboring cells interact
adhesion, communication/signals, metabolic
interactions
Example: sperm-egg fusion produces signals during
embryo development that prevent other competing
sperm from entering the egg
cell
cellConjugation Signalling
Surface receptor
Interactions
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Fibers of
extracellularmatrix (ECM)
Enzymatic
activity
Phospholipid
Cholesterol
CYTOPLASM
CYTOPLASM
Cell-cell
recognition
Glycoprotein
Intercellular
junctions
Microfilaments
of cytoskeleton
ATPTransport
Signal
transduction
Receptor
Signaling
molecule
Attachment to the cytoskeleton
and extracellular matrix (ECM)
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Membranes role # 7: Energy transduction
Sites of energy conversion
one form ofenergy alters to another
eg. membranes of chloroplasts and mitochondria
photosynthesis and cellular respiration
eg. rhodopsin proteins in cells of the eye
Light
retina
Human eye
Light energy gives
rhodopsin thepower to transport
ions across the
membrane
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Membranes role # 8: Flexibility and deformability
Changes in plasma membrane when cells
change shape cells crawling on a substratum
Changes in membrane organization when
vesicles pinch off from plasma membrane or
internal membranes
Amoeba proteus
Membranedeformations
during cell
division
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Chemical composition of
membrane
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Plasma membrane models
2013 John Wiley & Sons, Inc. All rights reserved.
1960s 1970s to date
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Major components: lipids and proteins
Lipids and proteins arrange in a lipid bilayer:
Act as the structural backboneof the membrane
Major component that estabilishes a permeability
barrier
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Membrane proteins: specific functions A lipid:protein ratio varies greatly depending on membrane
type and cell type
Membrane proteins can vary between differentmembranes or cell types depending on the function of themembrane
Carbohydrates (sugars) Glycolipids: sugars-attached lipids
Glycoproteins: sugar-attached proteins
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Lipid composition affects
membrane properties andmembrane protein function
Three major types: phospholipids,
sphingolipids, and sterols.
Lipid composition is different in
different membranes
Membrane lipids
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Phospholipids (phosphoglycerides) are the most abundant
membrane lipid.
Esterification of glycerol to:
-Phosphate
- Two fatty acids chains
Membrane lipid type # 1: Phospholipids
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Fatty (acyl) acid chains Are hydrophobic, unbranched hydrocarbons ~1620
carbons long. (eg. C16palmytate; C18sterate)
Fatty acid tails may be: polyunsaturated (>1 double bond)
monounsaturated (1 double bond eg. C18 oleate,C=C)
saturated (no double bonds)
H3C
COOH
COOHC10C12 C6C16
H3C C8
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Phospholipids are diverse in
head group and backbone
structure.
Usual additions to phosphate:
Cholinephosphatidylcholine
Ethanolamine
phosphatidylethanolamine
Inositolphosphatidylinosinol
HydrophilicHydrophobic
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Phospholipids: hydrophilic +
hydrophobic = amphipathic.
In membranes, phospholipids
are organized into lipid
bilayers with polar head
groups on each surface and
fatty acyl chains in the core
HydrophilicHydrophobic
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Phospholipids arrange into
a lipid bilayers that consist
of 2 leaflets
Polar head groups faceaqueous environment
Hydrocarbon tails form
hydrophobic inner core
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Membrane lipid type # 2: Sphingolipids
Sphingolipids play an important role in the nervous system and
are targets for infectious disease-causing microorganisms.
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Glycolipids: substituting a carbohydrate molecule onto
a ceramide.
CH2 C C CH
OHH2N
H H
CH (CH2)n CH3
CO R
Non-polar
HO+Sugar
Ceramide
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Glycolipids
Minor components of the membrane
ABO blood group antigens are glycolipids
Gal GlcNAc Gal Glu
Fuc
Gal GlcNAc Gal Glu
Fuc
Gal GlcNAc Gal Glu
Fuc
GlcNAc
Gal
O antigen
A antigen
B antigen
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Membrane lipid type # 3:
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Membrane lipid type # 3:
Sterols and similar compounds
50% of the membrane
smaller and less amphipathic than
other membrane lipids
campesterol
(plants: phytosterols)
cholesterol
(animals: zoosterols)
ergosterol
(fungi)
sterols
diploptene(bacteria: hopanoids)
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Cholesterol inserts between phospholipids: The small hydrophilic hydroxyl group faces the membrane
surface.
The rest is embedded in the lipid bilayer.
Its flat and rigid rings interfere with movement ofphospholipid fatty acid tails
Cholesterol decreases permeabilityand increases
durabilityof the membrane.
Cholesterols stiffenthe membrane
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Membrane lipids and fluidity
Phospholipids in a bilayer:
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Phospholipids in a bilayer:1. Flex and bend
2. Rotate
3. Diffuse laterally in the plane of the membrane4. Flip-flop from leaflet of the bilayer to the other leaflet
Occurs rarely on its own
Phospholipids can be found in different amounts in each leaflet ofthe membrane, with aid of special proteins called flippases
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SM: sphingomyelin
PC: phosphatidylcholine
PS: phosphatidylserine
PE: phosphatidylethanolamine
PI: phosphatidylinositol
Cl: cholesterol
2013 John Wiley & Sons, Inc. All rights reserved.
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1. Temperature
2. Acyl chain length
3. Acyl chain saturation
4. Sterol content
Mobility of lipid bilayers is
influenced many factors
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Factor # 1: Temperature
Lipid bilayers are more fluid at higher temperature due
to "melting" of lipid-lipid interactions Temperature at which phase transition occurs is
dependent upon the lipids present in the bilayertransition temperature
Temperature
Viscosity
Transition point: meltingtemperature (Tm)
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Factor # 2: Length of fatty acid acyl side chains
Viscosity
16-carbon fatty acidacyl chains
12-carbon fatty acid
acyl chains
Temperature
Tm Tm
Factor # 3: Unsaturated bonds
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Factor # 3: Unsaturated bonds
in fatty acid acyl chains
Saturated bonds decrease fluidity.
Unsaturated bonds increase fluidity.
Organization of saturated fatty acyl chains is more
regular than that of chains with unsaturated bonds.
Unsaturated bonds introduce "kinks" into the chains.
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kink in
chain due
to double
bond
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Viscosity
Temperature
16-carbon saturated
16-carbon mono-
unsaturated
Tm Tm
F t # 4 St l
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Factor # 4: Sterols
- At low temperatures: Cholesterol ring structures keep fattyacyl chains from interacting lowersmembrane viscosity
- At high temperatures: Cholesterol ring structures are more
rigid than fatty acyl chainsincreasesmembrane viscosity
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Membrane proteins
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Membrane Proteins
Carry out various functions in the membranes
Highly variable:
The amount of protein relative to lipid changes
between cell types and between different intracellular
membranes
Proteins may not be distributed homogenously
in membranes
eg. neuromuscular synapseapical-basal
membranes of epithelial cells Three types: integral, peripheral, and lipid-
anchored.
M b t i t # 1 I t l
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Membrane protein type # 1: Integral
Integral (intrinsic) proteinspass through lipid bilayer, and
cannot be removed withoutdistruption of the bilayer(detergents)
a) Single spanning
b) Multiple spanning
Transmembrane strand
M b t i t # 2 P i h l
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Membrane protein type # 2: Peripheral
Peripheral proteins:
- Are not inserted into thebilayer;
- Are found on either side
of the membrane;
- Interacts with
phospholipids or with
integral proteins.
- Can be removed by high
salt, low/ high pH, etc.
without disrupting bilayer
Membrane protein t pe # 3 Lipid anchored
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Membrane protein type # 3: Lipid-anchored
Lipid-anchored proteins do notpass all the way through the lipid
bilayer.
- Hydrophobic amino acid
groups allow proteins to insertinto internal (cytoplasmic)
leaflet
- Glycosylphosphatidylinositol
(GPI)-anchored proteins:covalently bonded to
phosphatidylinositol by
glycosylation.
P t i di t ib t d t i ll
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Proteins are distributed asymmetrically across
cellular membranes
Most sugar groupsof glycoproteins and glycolipids on
outer sideof plasma membrane
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Proteins can be mobile in lipid bilayers
Experiments showing that proteins are mobile in
membranes will be discussed in tutorials. Cellular membranes are considered to be fluid mosaics
ie. Molecules are not homogenously distributedinmembranes and most are mobile within the plane of themembrane.
Domains of cholesterol and sphinogomyleins can aggregatetogether to form lipid rafts.