M&R Membrane structure and dynamics

Question 1

What are the main functions of biological membranes?

Answer 1

For cells and organelles:

• highly selective permeable barrier
• control of enclosed chemical environment
• communication, between cells and their environment
• recognition, signalling molecules, adhesion proteins
• electrical and chemical signal generation in response to stimuli

Question 2

What is the composition of biological membranes? (with percentages)

Answer 2

40% lipid
60% protein
1-10% carbohydrate

Question 3

What are the main types of lipids in the membrane?

Answer 3

Predominant lipids are phospholipids
e.g. phosphatidylcholine (range of polar head groups)

Fatty acid chains - usually C16-18

Sphingolipids: Sphingomyelin
Only phospholipid not based on glycerol

Sphingolipids: Glycolipids
cerebrosides - the head group is a sugar monomer
gangliosides - the head group is an oligosaccharide

Cholesterol

Question 4

What are the modes of mobility of a lipid in a bilayer?

Answer 4

1. Flexion
2. Rotation
3. Lateral diffusion
4. Flip flop (rare)

Question 5

What are the modes of mobility of proteins in a bilayer?

What are the restraints on mobility of proteins within a bilayer?

Answer 5

1. Conformational change
2. Rotation
3. Lateral diffusion

NO FLIP FLOP

Lipid mediated effects- proteins tend to separate in cholesterol poor region
Some proteins are associated with peripheral proteins such as the cytoskeleton

Question 6

How do proteins associate with the lipid bilayer?

Answer 6

Peripheral proteins:
Bind to the surface by electrostatic and hydrogen bonds. Can be removed by changes in pH or ionic strength.

Integral proteins:
Interact extensively with the hydrophobic region of the bilayer. Can only be removed using detergents.

Question 7

Why is the asymmetrical orientation of some proteins important?

Answer 7

It is important for function e.g. a receptor for a hydrophilic messenger such as insulin needs to have the receptor on the extracellular side to be able to function

Question 8

How do membrane proteins contribute towards the cytoskeleton?

Answer 8

The erythrocyte cytoskeleton is a network of SPECTRIN and ACTIN molecules.
Spectrin is a long floppy rod molecule that is cross linked into a network by short actin filaments.
The spectrum-actin network is attached to the protein by ANKYRIN, attachment of integral proteins to the cytoskeleton restrict lateral mobility of the protein.

Question 9

What are haemolytic anaemias?

Answer 9

The erythrocyte cytoskeleton is important to maintain the deformity necessary for them to bend through capillary beds without lysis.
in heamolytic aneamia spectrin levels are depleted resulting in the RBC’s rounding up and being cleared by the spleen.

Question 10

How is protein orientation directed by membrane synthesis?

Answer 10

1. Membrane proteins synthesised in ribosomes
2. Hydrophobic N terminal signal sequence produced
3. Signal sequence recognised by SRP and synthesis stops
4. SRP directs ribosome to SRP receptors on RER
5. SRP dissociates
6. Synthesis continues and the new polypeptide is fed unto the ER
7. A highly hydrophobic stop transfer signal remains in the ER membrane
8. The rest of the synthesised protein is translated outside the ER in the cytoplasm so the proteins spans the membrane
9. The signal sequence is removed by signal peptidase

Question 11

What is the influence of cholesterol of membrane fluidity?

Answer 11

Makes the membrane less fluid by hydrogen bonding to fatty acid chains, reducing their motion

Makes the membrane more fluid by reducing phospholipid packing

Question 12

What is the evidence for membrane proteins?

Answer 12

Functional evidence:

• facilitated diffusion
• ion gradients
• specificity of cell responses

Biochemical evidence:

• gel electrophoresis
• freeze fracture