Phospholipids

Phospholipids are amphipathic molecules with a polar phosphate-containing head and hydrophobic fatty acid tails. They spontaneously assemble into bilayers in aqueous solution, forming the basic framework of all cell membranes.

Structure

A typical phospholipid has:

1. Glycerol backbone: a 3-carbon chain with three hydroxyls.
2. Two fatty acid tails: esterified to glycerol’s C1 and C2 hydroxyls.
3. Phosphate group: esterified to glycerol’s C3 hydroxyl.
4. Polar head group: connected to the phosphate by a second ester. Common head groups: choline (phosphatidylcholine, PC), ethanolamine (PE), serine (PS), inositol (PI).

The two fatty acid tails are hydrophobic (long hydrocarbon chains). The phosphate + head group is hydrophilic (charged, polar). This amphipathic structure is the chemical basis of membrane formation.

Charge at Physiological pH

The phosphate group carries a negative charge at pH 7. Head groups vary:

• Choline (+H₃N-CH₂CH₂-O-P-): positive quaternary ammonium, net phosphatidylcholine is zwitterion (net zero).
• Ethanolamine (H₃N⁺-CH₂CH₂-O-P-): similar zwitterion.
• Serine (HOOC-CH(NH₃⁺)-CH₂-O-P-): net -1 charge (COO⁻ at pH 7, NH₃⁺, P-).
• Inositol: neutral cyclohexanol-like ring with hydroxyls; net -1 from the phosphate.

Phosphatidylserine and phosphatidylinositol are the main anionic phospholipids in cell membranes.

Bilayer Assembly

In water, phospholipids assemble into structures that minimize contact between hydrophobic tails and water:

• Micelles: small spherical aggregates with tails pointing inward. Only for molecules with one hydrophobic tail (like soap, lysophospholipids).
• Bilayers: two-layer sheets with tails inward and heads facing water on both sides. The biological membrane. Favored for molecules with TWO hydrophobic tails (like standard phospholipids).
• Liposomes: bilayers curled into spherical vesicles.

The bilayer is ~5 nm thick. The tails are fluid (lateral diffusion is fast) but flip-flop (transfer from one leaflet to another) is very slow without enzyme assistance (flippases).

Membrane Fluidity

Membrane fluidity is affected by:

• Fatty acid tail length: longer tails = tighter packing = less fluid.
• Saturation: saturated tails pack tightly (low fluidity); unsaturated tails (cis double bonds) create kinks that prevent tight packing (high fluidity).
• Cholesterol: stiffens the membrane at high temperature (fills gaps, reduces fluidity) but prevents crystalline packing at low temperature (acts as a buffer).
• Temperature: higher T = more fluid.

Membrane Proteins

Membranes are not just lipid - proteins embedded in the bilayer act as transporters, receptors, and enzymes. About 25-50% of a typical cell membrane’s mass is protein. Protein topology (which side of the membrane each segment faces) is controlled during translation.

Biological Significance

Phospholipids enable:

1. Cell compartmentalization. Membranes separate cytoplasm from extracellular space and create organelles.
2. Selective permeability. The hydrophobic core is a barrier to polar molecules; channels and transporters provide controlled passage.
3. Signaling. Phosphoinositides (PIP₂, PIP₃) are key second messengers.
4. Energy generation. The inner mitochondrial membrane hosts the electron transport chain and ATP synthase.

Lipid Rafts

Specialized membrane microdomains enriched in cholesterol, sphingolipids, and certain proteins. Known as lipid rafts. They serve as platforms for signaling and protein sorting. An active area of biomedical research.