1c Membrane Structure

Cells synthesise new membranes by the expansion of preexisting ones.
Initial steps occur in the cytosol.
Fatty acid binding proteins: These chaperone the movement of lipids through the cell's intracellular space.
- They contain a hydrophobic pocket that covers the long-chain fatty acid, maintaining it in a hydrophobic environment.
Phospholipids are synthesised within the ER.
- They're initially inserted into the cytosolic side of the lipid bilayer.

Scramblases: Enzymes that facilitate the "flip-flop" of lipids.
- Allow lipids to move from the cytosolic side to the extracellular side.
- Ensure lipids are equally distributed on both sides of the membrane.

Membrane vesicles bud off from the ER and are transported to other parts of the cell.

In the Golgi apparatus, flippases ensure the correct placement of specific lipids.
Membranes are asymmetrical: Specific lipids are located on specific leaflets (sides) of the bilayer.
- Glycolipids are found only in the non-cytosolic half.
- Phosphatidylinositol is only in the cytosolic half.
- Phosphatidylserine is normally only on the cytosolic side, unless the cell is undergoing apoptosis.

Key Lipids:
- Phosphatidylcholine
- Sphingomyelin
- Phosphatidylethanolamine
- Phosphatidylserine

Phospholipid synthesis begins in the cytosol.
Chaperone proteins (fatty acid binding proteins) bring fatty acids to the ER membrane.
Phospholipids are added to the cytosolic half of the bilayer, causing curvature.

Scramblase catalyses the random transfer of phospholipids from one monolayer to the other.
This results in symmetrical growth of both halves of the bilayer.
Lipids are synthesised and inserted as a "cassette" into the cytosolic half, then equalised across both bilayers.

When membranes reach the Golgi apparatus, they encounter flippases.
Flippases selectively remove phosphatidylserine (green) and phosphatidylethanolamine (yellow) from the non-cytosolic monolayer and flip them to the cytosolic side.
These lipids are typically not present on the extracellular side of the cell membrane.
This transfer concentrates phosphatidylcholine (red) and sphingomyelin (brown) in the non-cytosolic monolayer.

The action of flippases causes a curvature in the opposite direction compared to the initial phospholipid insertion.
This curvature may drive vesicle budding within the Golgi.

Phospholipids are made in the ER and enter the cytosolic side of the bilayer.
Scramblase enzymes facilitate lipid flip-flop, resulting in symmetrical distribution.
Membrane vesicles are released and transported.
In the Golgi, flippases ensure lipids are on the correct side, leading to membrane asymmetry.

Lipid asymmetry is regulated by:
- Flippases: Actively translocate lipids to the cytoplasmic leaflet (inner).
- Flopases: Actively translocate lipids to the exoplasmic leaflet (outer).
- Scramblases: Promote equilibrium via a calcium-dependent mechanism; can move lipids in either direction.
Phospholipid translocases differ in:
- Lipid specificity
- Energy requirements
- Direction of translocation

Plasma membrane phospholipid asymmetry is maintained by the synchronous action of aminophospholipid flippase.
Selectively pumps phosphatidylserine and phosphatidylethanolamine to the inner layer (cytosolic side).
Flopases move phospholipids to the outer monolayer in a nonspecific way.
The mechanism of scramblase action (catalyzing diffusion) is less understood.

Uneven distribution across inner and outer membranes.
- Sphingolipids: More concentrated on the outside.
- Phosphatidylinositol: More concentrated on the inside (cytosolic side).

Sphingolipids:
- Have oligosaccharides attached to their polar heads.
- Oligosaccharides act as signaling agents.
- Placing them on the outside allows the oligosaccharides to point towards the extracellular fluid for cell communication.
Phosphatidylinositol:
- Phospholipase can cleave it to release inositol into the cytosol as a signal.
- Hence, higher concentration on the inner, cytosolic side.

Different cells have different lipid compositions in their plasma membranes (e.g., liver cell vs. red blood cell).
Bacterial plasma membranes (e.g., E. coli) are primarily composed of phosphatidylethanolamine.
Humans can convert phosphatidylethanolamine to phosphatidylcholine, but bacteria cannot, leading to the difference in composition.

Role of Cellular Membrane:
- Barrier separating the internal (cytosolic) side from the external environment.
- Facilitates communication between interior and exterior.
- Maintains shape and structure through interaction with the cytoskeleton.
Fluid Mosaic Model:
- Proteins are embedded within the phospholipid bilayer.
- Lateral movement of both phospholipids and proteins within each leaflet.
- Difficult for molecules to cross between leaflets due to the hydrophobic core.
- Asymmetric composition
Types of Membrane Lipids:
- Phospholipids
- Phosphoglycerides
- Sphingolipids
- Glycolipids
- Cholesterol
Membrane Synthesis:
- Begins in the cytosol.
- Proceeds through the ER (random distribution) and Golgi apparatus (specific distribution)
- Distributed to organelles or the plasma membrane.

When a lipid bilayer is torn, it reseals rather than forming a hemimicelle (cap).
Why?
- Energetically more favorable to reform a bilayer.
- Hemimicelle formation is difficult due to the shape of phospholipids and the hydrophobic fatty acid tails.
- If unable to heal, the membrane may form two vesicles.