MEMBRANE LIPID COMPOSITION

 Types of Membrane Lipids

•    Lipids make up ~50% of most animal cell membrane mass. All membrane lipids are amphiphilic — they have a hydrophilic (polar) head and hydrophobic (nonpolar) tails. A typical red blood cell membrane contains ~7 × 10⁸ lipid molecules.

Lipid Class

Backbone

Key Features

Glycerophospholipids

Glycerol

Two fatty acid tails via ester bonds; examples: PC, PE, PS, PI, PG

Sphingolipids

Sphingosine

One fatty acid via amide bond; sphingomyelin (SM) has phosphocholine head

Glycolipids

Sphingosine (animals)

Sugar attached instead of phosphate; exclusively on outer leaflet

Sterols

Rigid 4-ring structure

Cholesterol (animals), ergosterol (fungi), sitosterol/brassicosterol (plants)

Plasmalogens

Glycerol

Ether-linked alkene at sn-1 position (not ester-linked)

 Fatty Acid Tails and Melting Temperature (Tm)

•    The length and saturation of fatty acid tails determine the membrane's phase transition temperature (Tm).

•    Longer chains → higher Tm (more van der Waals interactions). Unsaturated chains (cis-double bonds) → kinks → lower Tm (prevent tight packing).

Phosphatidylcholine Type

Tm (°C)

DSPC (Di 18:0 — two saturated C18)

+58

DPPC (Di 16:0 — two saturated C16)

+41

SOPC (18:0, 18:1 — one unsaturated)

+3

DOPC (Di 18:1 — two unsaturated)

−22

 Tm is measured by Differential Scanning Calorimetry (DSC). Order from highest to lowest Tm: DSPC > DPPC > POPC (SOPC) > DOPC.

Cholesterol — The Fluidity Buffer

•    Cholesterol is the most abundant sterol in animal cell membranes (35–45% of plasma membrane lipid). It inserts between phospholipids with its hydroxyl group near the polar heads and its rigid ring system among the fatty acid tails.

•    At high temperature: cholesterol stiffens the membrane by restricting phospholipid movement → reduces fluidity.

•    At low temperature: cholesterol prevents crystallisation by disrupting regular packing → maintains fluidity.

•    Overall effect: cholesterol buffers fluidity — broadens the phase transition and decreases permeability to small water-soluble molecules.

CHOLESTEROL DISTRIBUTION across organelles:

•    Plasma membrane (35–45%) >> Lysosomal membrane > Smooth ER (5–8%) >> Inner mitochondrial membrane (lowest)

•    Smooth ER is the SITE of cholesterol synthesis but maintains LOW levels to preserve fluidity for biosynthesis.

•    StAR protein transports cholesterol from outer to inner mitochondrial membrane in steroidogenic cells.

•    Cholesterol is ABSENT from most prokaryotic and plant cell membranes (exception: Mycoplasma membranes contain sterols).

Phospholipid Composition Varies by Membrane

Membrane

Major Phospholipids

Distinctive Feature

Rat liver plasma membrane

PC > SM > PS > PE > PI

High cholesterol, sphingomyelin

E. coli plasma membrane

PE > PG > cardiolipin (DPG) > PS

No phosphatidylcholine, No sphingomyelin

Inner mitochondrial membrane

PC > PE > PS > PI

High cardiolipin (DPG) — essential for ETC Complexes

 

Phospholipid Asymmetry

•    The two leaflets of the bilayer have different lipid compositions. In red blood cells:

Leaflet

Major Phospholipids

Enriched Feature / Functions

Outer (exoplasmic)

PC + SM (choline-containing)

Glycolipids always outer; forms lipid rafts

Inner (cytosolic)

PS + PE (charged)

PS activates PKC; PI phosphorylation → signalling → PIP2 → IP3 + DAG via PLC

 

MAINTAINING ASYMMETRY — Three enzymes:

•    Flippase: ATP-dependent; moves PS and PE from outer → inner leaflet (inward)

•    Floppase: ATP-dependent; moves lipids from inner → outer leaflet (outward)

•    Scramblase: ATP-independent; moves any lipid bidirectionally down concentration gradient

During APOPTOSIS: scramblase is activated, flippase is inactivated → PS is exposed on the outer surface → "eat me" signal → recognised by macrophages → phagocytosis.

Glycolipids

•    Glycolipids are sugar-containing lipids found exclusively on the outer leaflet of the plasma membrane. In animal cells, they are built from sphingosine (like sphingomyelin). They self-associate via hydrogen bonds and van der Waals forces, partitioning into lipid rafts with cholesterol.

Type

Details

Cerebrosides

Simple glycolipids with a single sugar (galactose or glucose) linked to ceramide

Gangliosides

Complex glycolipids with sialic acid (negative charge); abundant in nerve cells (5–10% of total lipid); GM1 is the receptor for cholera toxin

 

•    Cholera toxin binds GM1 ganglioside → activates adenylyl cyclase → ↑cAMP → opens CFTR Cl⁻ channels → Cl⁻ and water loss → dehydration.

•    ORT (oral rehydration therapy) uses glucose + NaCl to leverage the Na⁺-glucose cotransporter (SGLT), creating an osmotic gradient that drives water absorption back into the blood.

Lipid Rafts and Caveolae

•    Lipid rafts are dynamic membrane microdomains enriched in sphingolipids + cholesterol. Cholesterol fills the voids under the large sphingolipid head groups, stabilising the raft. Sphingolipids have slightly higher mutual affinity for cholesterol than other lipids, causing them to aggregate. PS is NOT a raft component (it resides on the inner leaflet).

•    Caveolae are small flask-shaped invaginations of the plasma membrane composed of cholesterol + sphingolipids + caveolins (integral membrane proteins, on the inner leaflet). Functions: endocytosis, signal transduction, calcium signalling in cardiac muscle cells.

Lipid Droplets and Lipoproteins

•    Lipid droplets form in the ER membrane and have a phospholipid monolayer (not bilayer) surrounding a hydrophobic core.

•    Similarly, lipoproteins (VLDL, IDL, LDL, HDL, chylomicrons) are covered by a phospholipid monolayer + apolipoproteins.

•    In contrast, endocytic vesicles and other membrane-bound organelles are enclosed by a standard lipid bilayer.