1. Cell Membrane Structure and Function

2. Cystic Fibrosis
•most common autosomal recessive disease affecting Caucasian populations
•incidence of 1 in 2000 births
•Clinical features
•pulmonary obstruction and infection
•recurrent and persistent infections
•exocrine pancreatic dysfunction
•infertility, especially in males

3. Diagnosis
failure to thrive -child fails to gain weight despite a good appetite
sweat test -chloride concentration greater than 60 meq/liter
life expectancy now often >30 years
this was the disease most people thought would be a good candidate for gene therapy

4. Metabolic Basis of Disease
defect in a single gene on chromosome 7 that encodes a cAMP-regulated chloride channel
called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
resides on the apical surface of epithelial cells lining the airways, intestines, vas deferens, sweat ducts, and pancreatic ducts

5. Genetics and Epidemiology
autosomal recessive
4-5% of Americans have at least one CF allele
>900 different mutations (.F508, ~70% of CF alleles)
~50% of the patients are homozygous for the .F508 mutation

6. Consequences of Disease
Loss of CFTR function
fluid secretion is insufficient
protein portions of the secretions become viscous
results in obstruction in the ducts and eventual organ dysfunction

7. Lung Disease
accounts for much of the morbidity and nearly all the mortality from the disease
bacterial infections become soon after birth, and remain difficult to stop
Pseudomonas aeruginosais the main agent in patients 18 or older
bacterial resistance to antibiotics results in mucoid coating of lungs, and subsequent decline in lung

8. Cystic Fibrosis

9. Membrane Functions
Isolate the cell’s contents from the external environment
Regulate traffic in and out of the cell
Communicate with other cells

10. Plasma membrane structure and functions
The phospholipid bilayer and isolation
Impermeable to water-soluble and polar molecules, ions
Permeable to small and nonpolar molecules
Lipids oriented with polar heads facing out

11. tails (hydrophobic) head (hydrophilic)
Figure: 03-00UN01
Title:
A phospholipid.
Caption:
A phospholipid has a polar hydrophic head and a pair of nonpolar hydrophobic tails.
tails
(hydrophobic)
head
(hydrophilic)

12. extracellular fluid (watery environment) phospholipid hydrophilic
heads
hydrophobic
tails
bilayer
Figure: 03-00UN02
Title:
Phospholipid bilayer.
Caption:
hydrophilic
heads
cytoplasm
(watery environment)

13. Membrane Structure and Function
Membranes are “fluid mosaics” with proteins embedded in or attached to the membrane
Proteins can move within the fluid lipid bilayer

14. extracellular fluid (outside)
recognition protein
receptor protein
transport protein
binding site
phospholipid
bilayer
carbohydrate
cholesterol
phospholipid
Figure: 03-01
Title:
The plasma membrane is a fluid mosaic.
Caption:
The plasma membrane is a bilayer of phospholipids in which various proteins are embedded. Many proteins have carbohydrates attached to them. The wide variety of membrane proteins fall mostly into three categories: recognition proteins, receptor proteins, and transport proteins.
protein filaments
cytoplasm (inside)

15. Types of Membrane Proteins
Transport proteins
regulate the movement of water-soluble molecules across the membrane
Channel proteins
Carrier proteins

16. Types of Membrane Proteins
2. Receptor Proteins
trigger cellular response when specific molecules bind to them
Nervous system
Endocrine system

17. Types of Membrane Proteins
3. Recognition proteins
act as ID tags and cell surface attachment sites
the immune system

18. Transport across membranes
Passive transport is a function of molecular size, lipid solubility, and size of the concentration gradient
1. Simple diffusion

19. 2 Dye molecules diffuse into the water; water 3 Both dye molecules
into the dye.
3 Both dye molecules
and water molecules
are evenly dispersed.
1 A drop of dye is
placed in water.
drop of dye
Figure: 03-02
Title:
Diffusion of a dye in water.
Caption:
pure water

20. (extracellular fluid)
(a) simple diffusion
(extracellular fluid)
Figure: 03-04a
Title:
Diffusion through the plasma membrane.
Caption:
(a) Lipid-soluble molecules and gases such as oxygen and carbon dioxide can pass by simple diffusion directly through the phospholipids.
(cytoplasm)

21. Transport across membranes
Passive transport…(cont.)
2. Osmosis
a. Isotonic
b. Hypertonic
c. Hypotonic

22. selectively permeable membrane
H2O
selectively
permeable
membrane
free water
molecule: can
fit through pore
sugar
pore
bound water molecules
clustered around sugar:
cannot fit through pore
Figure: 03-03
Title:
Osmosis.
Caption:
Free water molecules diffuse down their concentration gradient across a selectively permeable membrane, from a region of high water concentration to a region of lower water concentration.
(b)
selectively permeable
membrane
sugar molecule
bag
bursts
water molecule
pure water

23. (b) hypertonic solution (c) hypotonic solution
10 micrometers
(a) isotonic solution
(b) hypertonic solution
(c) hypotonic solution
Figure: 03-05
Title:
The effects of osmosis.
Caption:
Red blood cells are normally suspended in the fluid environment of the blood. (a) If red blood cells are immersed in an isotonic salt solution, which has the same concentration of dissolved substances as the blood cells do, there is no net movement of water across the plasma membrane. The red blood cells keep their characteristic dimpled disk shape. (b) A hypertonic solution, with too much salt, causes water to leave the cells, shriveling them up. (c) A hypotonic solution, with less salt than is in the cells, causes water to enter, and the cells swell.
equal movement of water
into and out of cells
net water movement
out of cells
net water movement
into cells

24. Transport across membranes
Passive transport…(cont.)
3. Facilitated diffusion

25. (b) facilitated diffusion through a channel
proteins forming
permanent
hydrophilic channel
ions
Figure: 03-04b
Title:
Diffusion through the plasma membrane.
Caption:
(b) Some water-soluble molecules enter or exit the cell by facilitated diffusion through a channel protein.
channel
protein

26. amino acids, sugars, small proteins
(c) facilitated diffusion through a carrier
amino acids,
sugars,
small proteins
(extracellular fluid)
Figure: 03-04c
Title:
Diffusion through the plasma membrane.
Caption:
(c) Certain molecules cross a membrane by facilitated diffusion through a carrier protein that changes shape to allow the passage.
carrier
protein
(cytoplasm)
Carrier protein has binding site for molecule.
Molecule enters binding site.
Carrier protein changes
shape, transporting molecule
across membrane.
Carrier protein resumes original shape.

27. Transport across membranes
Energy-requiring transport
1. Active transport
Ion gradients and energy production
Endocytosis
Exocytosis

28. ATP binding site recognition site
(extracellular fluid)
transport protein
Figure: 03-06
Title:
Active transport.
Caption:
Active transport uses cellular energy to move molecules across the plasma membrane, often against a concentration gradient. An active-transport protein binds ATP and the molecule to be transported, and then changes shape to move the ion across the membrane.
ATP binding site
recognition
site
ATP
Transport protein resumes original shape.
Transport protein uses energy from ATP to change shape and move
ion across membrane.
Transport protein binds ATP and Ca2+.
Ca2+
(cytoplasm)

29. (extracellular fluid)
pinocytosis
(extracellular fluid) 1 3 3 2
vesicle containing
extracellular
fluid
(cytoplasm)
Figure: 03-07
Title:
Two types of endocytosis.
Caption:
(a) To capture drops of liquid, a dimple in the plasma membrane deepens and eventually pinches off as a fluid-filled vesicle, which contains a random sampling of the extracellular fluid. (b) Pseudopodia encircle an extracellular particle. The ends of the pseudopodia fuse, forming a large vesicle that contains the engulfed particle.
cell
(b)
phagocytosis
food particle
pseudopod 1 2 3
particle
enclosed in vesicle

30. secreted material plasma membrane plasma membrane 3 2 1
(extracellular fluid)
plasma membrane
plasma membrane 3 2 1
Figure: 03-08
Title:
Exocytosis.
Caption:
Exocytosis is functionally the reverse of endocytosis. The material to be ejected from the cell is encapsulated into a membrane-bound vesicle that moves to the plasma membrane and fuses with it. After the vesicle opens to the outside, its contents leave by diffusion.
vesicle
(cytoplasm)
0.2 micrometer

31. Figure: 03-T01
Title:
Transport across membranes.
Caption: