What are the main functions of a biological membrane?
- Continuous, highly selective permeability barrier
- Allows control of the enclosed chemical environment
- Communication (can control the flow of information between cells and their environment)
- Recognition (signalling molecules, adhesion proteins, immune surveillance)
- Signal generation in response to stimuli (electrical or chemical)
Different membranes have specialised functions too
Describe the composition of biological membranes
Varies depending on source
Dry weight : approx. 40% lipid, 60% protein and 1-10% carbohydrate
20% of the total membrane weight is water
What are the modes of mobility for lipid molecules in a lipid bilayer?
- Intra-chain rotation: kink formation of the fatty acyl chain
- Fast-axial rotation
- Fast-lateral diffusion within the plane of the bilayer
- Flip-flop: movement of lipid molecules from 1 half of the bilayer to the other on a 1-for-1 exchange basis
How can unsaturated hydrocarbon chains affect fluidity?
If they have cis double bonds, they can disrupt phospholipid packing, which helps to maintain fluidity
What are the main types of lipids?
- Membrane lipids (amphipathic molecules)
- Phospholipids (head group and fatty acid chain)
- Sphingomyelin (only phospholipid not based on glycerol)
- Predominant lipids
- Glycolipids
What are the different types of glycolipids?
- Cerebroside: only has a single sugar monomer head group
- Ganglioside: has complex carbohydrate head groups
Describe lipid bilayer formation
- Amphipathic molecules form 1 of 2 structures in water (micelles and bilayers)
- Bilayers are the favoured structure for phospholipids and glycolipids in aqueous media
- Bilayer formation is spontaneous in water
- Formation is driven by van der Waals
- The structure is stabilised by non-covalent forces
What is the permeability of the lipid bilayer?
It has a very low permeability to ions and most polar molecules
What is the effect of cholesterol on membrane stability?
- Can reduce the fluidity since it attaches itself, a rigid molecule, to a phospholipid hence reducing movement
- Can increase the fluidity by affecting the phospholipid packing
- At higher temperatures, cholesterol decreases membrane fluidity; at lower temperatures it increases membrane fluidity.
Describe the structure of cholesterol
- Polar head group
- Rigid planar steroid ring structure
- Non-polar hydrocarbon tail
How can membrane proteins associate with the lipid bilayer?
Peripheral =
- bound to surface
- electrostatic and hydrogen bond interactions
- removed by changes in pH or in ionic strength
Integral =
- interact extensively with hydrophobic domains of the lipid bilayer
- cannot be removed by manipulation of pH and ionic strength
- are removed by agents that compete for non-polar interactions
What evidence is there for membrane proteins?
Functional: - Facilitated diffusion - Ion gradients - Specificity of cell responses Biochemical: - Membrane fractionation and gel electrophoresis - Freeze fracture
How can membrane proteins move?
- Conformational change
- Rotational
- Lateral
- NO FLIP-FLOP
How can membrane protein mobility be restricted?
- Aggregates
- Tethering (to membrane or to cytoskeleton)
- Interaction with other cells
- Lipid mediated effects
How do membrane proteins contribute to the erythrocyte cytoskeleton?
- The peripheral membrane proteins compose a membrane skeleton on the cytoplasmic face of the membrane
- This cytoskeleton holds the shape of the RBCs
- Composed of the protein spectrum and actin molecules
- This actin-spectrin network is attached to the membrane by adaptor molecules (ankyrin and glycophorin)
- Attachment of integral membrane proteins to the cytoskeleton restricts material mobility of the membrane protein
How are integral membrane proteins inserted into membranes?
- They are synthesised against the mRNA template by ribosomes
- The signal sequence at the N-terminus is recognised by a signal recognition particle (SRP)
- Binding of the SRP to the growing polypeptide chain and the ribosome locks the ribosome complex and prevents protein synthesis while the ribosome is in the cytoplasm
- On the ER, the SRP is recognised by a SRP receptor
- In making the intersection with the SRP receptor, the SRP is released from the signal sequence
- Further synthesis is directed into the lumen of the ER, as the ribosome is anchored to a pore complex
- The protein contains a ‘stop transfer signal’, which is highly hydrophobic
- It forms the transmembranous region of the protein and causes the rest of the protein to be translated in the cytoplasm
- A lateral gating mechanism releases the membrane protein from the protein translator into the lipid bilayer
- The ribosome detaches
- Signal sequence is cleaved by signal peptidases
Hence, a transmembrane protein with its N-terminus directed into the lumen and its C-terminus directed into the cytoplasm is produced.
What is hereditary spherocytosis?
A haemolytic anaemia
- Spectrin is depleted by 40-50%
- Erythrocytes round up
- Less resistant to lysis
- Cleared by spleen
What is hereditary elliptocytosis?
A haemolytic anaemia
- Defect in spectrin molecules
- Unable to form heterotetramers
- Fragile elliptoid cells
What are some properties of transmembrane domains?
- Usually 18-22 amino acids long
- The amino acids have hydrophobic R-groups
- Have an alpha-helix usually
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Week 1 - Biological membranes19
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Week 10 - ANS12
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Week 2 - Role of membranes as permeability barriers34
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Week 3 - The Resting Membrane Potential18
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Week 4 - Action Potential and Conduction of the Nerve Impulse28
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Week 5 - Effects of Electrical Signals21
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Week 6 - Receptors in cell signalling, principles of receptor-mediated endocytosis35
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Week 7 - Receptor-Effector signalling31
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Week 8 - Drugs and Receptors29
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Week 9 - Pharmacokinetics18
