Examples of lipid and protein domains in cell membranes
Single domains, enriched
in the fluorescent lipid
Lipid domains with greater
relative order than the
bulk membrane, visualized
in living macrophages with
the fluorescent probe,
The warmer pseudocolours represent
more ordered regions
Domains formed by the
The scale bars represent 1 μm in a, and 5 μm in c and d.
Types of lipid rafts: Two
• Caveolae: small, flaskshaped invaginations of
the plasma membrane
enriched in caveolin
• Planar lipid rafts: found in
neurons and enriched in
• Caveolin and flotillin recruit
• Signaling can be promoted
Why do they form? Cholesterol
• Cholesterol is the
dynamic “glue” that holds
the raft together
– Hydroxyl H-bonding
• Up to 25% of cholesterol
is found in the
• When removed, most
proteins dissociate from
Disorders & Diseases
• HIV virus
– Budding may occur from
• Mood disorders
– Therapeutic efficacy of antidepressants
• Alzheimer’s disease
– Platforms for production of amyloid-β (neurotoxic
• Prion disorder
– Normal prion protein (PrPc) is converted to abnormal
proteins (PrPsc) in lipid rafts (GPI anchor required)
Why all the controversy?
• Problems with biomembranes
– Lipid rafts are too small to be resolved by light
– Difficult to study lipid rafts in intact cells
– Not in thermodynamic equilibrium
• Problems with synthetic membranes
Lower concentration of proteins
Difficult to model membrane-cytoskeletal interactions
Lack natural lipid asymmetry
Studied under equilibrium conditions
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Video: Viel, A., Lue R.A., “Inner life of the cell.” The president and Fellows of Harvard College