A Closer Look at Membranes Cystic Fibrosis

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A Closer Look at Membranes
Chapter 5
Cystic Fibrosis
• Caused by defective protein
channel (CFTR) in epithelial cells
• Not enough Cl- and water cross
membranes
• Thick mucus clogs airways and ducts
throughout body
• Usually fatal by early adulthood
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More on CF ……
• The protein is not functional, and in some
cases may be degraded
• There are MANY ways the protein can not
work (it has 1500 amino acids) – at least 500
different versions that don’t work have been
found
• Most people with CF have the ∆F508
mutation (one amino acid, the phenylalanine
at position #508 is deleted)
Membranes, and membrane proteins, control the
flow of molecules and information between the
inside and the outside of the cell ….
…which is really important!
Lipid Bilayer
• Main component of
cell membranes
• Fatty acid tails
sandwiched
between hydrophilic
heads
lipid
bilayer
cytoplasm
• Gives membrane its
fluid properties
Figure 5.2c
Page 82
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Fluid Mosaic Model
• Membrane is a mosaic of
– Phospholipids
– Glycolipids
– Sterols
– Proteins
• Most phospholipids and some proteins
can drift through membrane (fluid)
Membrane Proteins
Integral membrane proteins have a part that is
embedded in the membrane – hydrophobic anchor.
adhesion
protein
receptor
protein
communication
protein
recognition
protein
passive
transporter
active transporters
Figure 5.5
Page 85
Membrane Experiments
• Split membranes reveal embedded
proteins (freeze fracture technique)
In-text figure
Page 86
3
Membrane Experiments
• Hybrid human-mouse cell shows some
proteins drift within membrane
human cell
mouse cell
hybrid cell
Figure 5.6
Page 86
Another view:
URL: How Cytochemists Study
Membranes
Gwen V. Childs, Ph.D.
childsgwenv@uams.edu
© copyright 1995 Gwen V.
Childs, Ph.D.
Another
experiment
showing fluidity
of the membrane
How Cytochemists Study
Membranes
Gwen V. Childs, Ph.D.
childsgwenv@uams.edu
© copyright 1995 Gwen V.
Childs, Ph.D.
4
Selective Permeability
glucose and other large, polar,
O2, CO2,
and other small, non-polar water-soluble molecules; ions,
water molecules
molecules; some water
molecules
Ways for molecules to to
cross membranes
Diffusion across lipid bilayer
Passive transport
Active transport
Endocytosis
Exocytosis
Concentration Gradient
• Means that the number of molecules or ions
in one region is different than the number in
another region
• Movement of molecules from an area of
higher concentration, to an area of lower
concentration = “down” the gradient
• Think of something with an odor – molecules
moving in air, more concentrated closer to the
source, they diffuse away from the source
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Diffusion
• The net movement of like molecules or
ions down a concentration gradient
• Although molecules collide randomly,
the net movement is away from the
place with the most collisions (down
gradient)
Example of Diffusion
Equilibrium
Factors Affecting Diffusion Rate
• Steepness of concentration gradient
– Steeper gradient, faster diffusion
• Molecular size
– Smaller molecules, faster diffusion
• Temperature
– Higher temperature, faster diffusion
• Electrical or pressure gradients
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Transport Proteins
• Span the lipid bilayer
• Interior is able to open to both sides
• Change shape when they interact
with solute
• Move water-soluble substances
across a membrane
Passive and Active Transport
Passive Transport
Active Transport
• Doesn’t require energy
inputs
• Requires ATP
• Solutes diffuse through
a channel inside the
protein’s interior
• Net movement is down
concentration gradient
• Protein is an ATPase
pump
• Pumps solute against its
concentration gradient
Passive Transport
glucose transporter
solute (glucose)
high
low
Stepped Art
Figure 5.10
Page 88
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ATPase ?
• The ending “ase” means:
an enzyme; this one cleaves ATP
• ATP can be converted to:
– ADP + Pi (adenosine diphosphate + inorganic PO4)
– AMP + PPi (adenosine monophsphate)
• The bonds between the phosphate groups
are high energy bonds
– when they are broken, the energy released can be
used to do other things (like help a molecule move
against its concentration gradient)
higher calcium
concentration
Active Transport
lower calcium concentration
ATP
Pi
ADP
Stepped Art
Figure 5.11
Page 89
Osmosis
• The diffusion of water molecules down
its own concentration gradient, across
a selectively permeable membrane
• Solutions with higher concentrations of
solutes (ions, sugar, etc) have lower
concentrations of water.
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Hypotonic vs. Hypertonic Solutions
• We talk about solutions in terms of their
solute concentration
• Tonicity refers to relative solute
concentrations
– Hypertonic means higher salt (a 40% solution of
sucrose is hypertonic with respect to a 10%
solution (hyper means above: hyperactive)
– Hypotonic means lower salt: a 10% solution is
hypotonic relative to a 40% solution (hypo means
under: a hypodermic needle gets under the skin)
More on osmosis ….
• So… water will move
– from the hypotonic solution (10% solute, 90% water)
– to the hypertonic soution (40% solute, 60% water)
– it will move from higher to lower water concentration
• One way to remember this is that red blood cells
swell and burst when put water – this is called
“osmotic lysis” (you should see it in lab).
– Normal blood has a lot of solutes (including about
0.9% NaCl)
– Pure water is as hypotonic as you can get, so the cell
is hypertonic (compared with water).
Tonicity
2% sucrose
solution
distilled water
10%
sucrose
solution
2%
sucrose
solution
Hypotonic
Conditions
Hypertonic
Conditions
Isotonic
Conditions
Figure 5.13
Page 90
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Fluid Pressure
• Hydrostatic pressure
– The pressure any volume of fluid exerts
against a wall
• Osmotic pressure
– The amount of force preventing further
increase in a solutions volume
– Osmotic lysis example: red blood cells in
water
• Turgor pressure vs Plasmolysis
normal plant cells
(note central vacuole full of fluid)
after plasmolysis –
these would be wilted
Exocytosis
plasma membrane
Endocytosis and
Exocytosis
cytoplasm
Endocytosis
cytoplasm
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Endocytosis Pathways
• Bulk phase
• Receptor-mediated
• Phagocytosis
clathrin
Membrane
Cycling
clathrin
Exocytosis and
endocytosis
continually
replace and
withdraw patches
of plasma
membrane
Figure 5.19
Page 93
Figures 5.17, 5.18
Pages 92, 93
Golgi
body
lysosome
Phagocytosis
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Signal Proteins
Membrane proteins can also transmit
signals across membranes, even if no
molecules are actually transported
Interaction of a
membrane
receptor with its
hormone, at the
outside of the
cell, may cause
it to change its
shape, and now
do something on
the inside of the
cell
Summary of key points
• Membranes form a fluid but hydrophobic
barrier to the movement of molecules in and
out of the cell
• Proteins in the membrane control access to
the inside of the cell, and also permit
molecules to leave the cell in a controlled way
• Some membrane crossing (transport) events
are passive, but some require energy (active)
• Membrane proteins also can transmit
molecular signals across membranes, even
when no molecules are actually transported
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