1b Membrane Structure

Phosphoglycerides:
- Form three of the four major phospholipids in the cellular membrane.
- Derived from glycerol.
- Different head groups are represented by different colors/symbols.
(a) Phosphatidylcholine:
- Most abundant phospholipid in eukaryotic cell membranes.
- Source of diacylglycerol, which plays a major role in cellular signaling.
(b) Phosphatidylserine:
- Major anionic phospholipid class found in the inner leaflet of the plasma membrane.
- Plays key roles in signaling pathways.
- Normally confined to the cytoplasm side (interior of the cell).
- Can be moved to the outside via scramblase.
- In apoptosis, phosphatidylserine moves to the outer membrane, signaling phagocytes for cell death and phagocytosis.
(c) Phosphatidylethanolamine:
- Second most abundant phospholipid in human membranes.
- Primary phospholipid in bacterial cell membranes.
- Humans can convert phosphatidylethanolamine into phosphocholine, bacteria cannot.
- Carries a net negative charge and interacts with positively charged membrane proteins.
Phosphatidyl structure:
- From the phosphate group downwards, structures are the same among phosphoglycerides.
- The "phosphatidyl" part refers to phosphate, glycerol, and fatty acid tails.
- The head group (choline, serine, etc.) is the variable part.

Second major class of lipids in the membrane.
Built on sphingosine backbone (an amino alcohol) rather than glycerol.
Sphingosine:
- Amino alcohol with a long unsaturated hydrocarbon chain.
- Requires the addition of one fatty acid to be suitable for inclusion in the cellular membrane.
Mainly found in brain and neurons.
Present only on the noncytosolic side (outer leaflet) of the bilayer.
Sphingomyelin: Found in the myelin sheath around nerve axons.
Myelin:
- Allows rapid transmission of nerve impulses.
- Enables smooth, rapid, coordinated movements.
Damage to myelin can cause degenerative diseases (e.g., multiple sclerosis, which is demyelination).

Class of lipids sharing a basic ring structure (four rings).
- Three fused six-carbon atom rings and one five-carbon atom ring.
Ergosterol:
- Present in yeast but not humans.
Phytosterols:
- Present in plants (e.g. stigmata sterol).
Differences between animal and fungal sterol biosynthesis are targets for antifungal drugs.
Sterols are amphipathic:
- Hydroxyl group is the polar group.
- Cannot form a bilayer by themselves.
- Intercalate between phospholipid molecules in the bilayer.
Role:
- Provide structural support.
- Prevent too-close packing of phospholipid hydrocarbon tails.
- Help maintain membrane fluidity and stability.

Forms a sealed, closed compartment without free edges.
Tears in the membrane are rapidly repaired to prevent hydrocarbon tails from contacting the aqueous layer (energetically unfavorable).
Encloses two sides:
- Internal (cytoplasmic) face
- External face (facing extracellular space)
Organelles structured similarly:
- Exoplasmic face (facing inside the organelle)
- Cytoplasmic face (facing the cytoplasm of the cell)
Organelles with double membranes:
- Nucleus, mitochondria, chloroplasts
- External face of both membranes faces the intermembrane space.

They can:
- Rotate
- Are flexible
- Move in position.
- Diffuse laterally along the lipid bilayer.
Rarely move from one leaflet (e.g., internal to external) without enzyme assistance.
Phosphatidylserine is an exception in apoptotic cells where this "flip-flop" is enabled.
Cholesterol can move between layers rapidly.

Bilayer of lipids containing proteins.
Held together by noncovalent bonds.
Asymmetrical composition:
- Different lipid and protein composition on the cytoplasmic vs. exterior side.
Fluid structure:
- Proteins and lipids can diffuse laterally (along the bilayer not across it) very rapidly.
- Example: can diffuse across the length of a bacteria cell (2 micrometers) in a second.
Hydrophobic residues within integrated proteins embed within the bilayer (e.g., arginine, tyrosine, aspartic acid).
Hydrophilic amino acid residues (e.g., glycine, alanine, valine) constitute parts of the protein outside the cell membrane.

Cholesterol fits within gaps between phospholipid molecules and regulates membrane fluidity.
Sits within the hydrophobic section of the bilayer.
Bilayer at different temperatures:
- Low temperature: gel phase.
- Hydrocarbon tails tightly packed.
- Less fluidity.
- Less ability to rotate or diffuse laterally.
- Body temperature: melting of the bilayer.
- Movement can happen.
- Phospholipids can rotate and diffuse laterally across the membrane.
Cholesterol restricts random movement of phospholipid heads on the outer surface, stabilising the bilayer.
Prevents tight packing and allows fluidity.
Effect depends on cholesterol concentration:
- Low concentration: steroid ring separates and disperses phospholipid tails, increasing fluidity.
- Warm temperature: restrains phospholipid movement, stabilizing but maintaining fluidity by preventing tight packing.
Cholesterol causes the membrane to stiffen because the cholesterol molecules insert themselves to fill spaces between the acyl chains.
As a consequence, thermal movement is reduced, the thickness of the bilayer increases, and fewer water molecules venture into the hydrophobic core.
Membranes containing cholesterol are stiffer and less permeable.