Biophysical studies of membrane proteins/peptides. Interaction with ...

INTRODUCTION: BIOMEMBRANES
Figure 1.3 – Structure of cholesterol (From Berg et al., 2002).
1.3. Lipid asymmetry across the bilayer
Lipid composition in the cytoplasmatic and exoplasmatic leaflets of the bilayer is
asymmetric. In plasma membranes, the cytoplasmatic leaflet is enriched in PE, PS, and
PI, while in the exoplasmatic leaflet lipids like PC, glycolipids, sphingomyelin and
cholesterol exist in higher concentrations.
One of the factors contributing to this lipid asymmetry is the site of synthesis of the
lipids in the membranes of the endoplasmic reticulum and Golgi, as it dictates the
plasma membrane leaflet where the lipid is to be inserted. In this way, addition of
carbohydrates to glycolipids is done through the luminal side of the Golgi apparatus that
is topologically equivalent to the exterior of the cell. This however does not account for
all asymmetry observed and the action of ATP-powered transport proteins called
translocases is essential (Lodish et al., 2000).
However, asymmetry would be lost if lipids easily crossed from one leaflet to the
other. In fact, in protein free liposomes, the kinetics of this process is extremely slow,
on the order of hours/days. This is due to the extremely energetically unfavourable
process of inserting the polar headgroup of a lipid in the hydrophobic membrane
interior.
Lipid asymmetry is of functional importance, and many cytosolic proteins bind to
specific lipid headgroups (like PS or PI) in the cytosolic leaflet of the bilayer. Animals
also use phospholipid asymmetry in the plasma membrane of cells as a control to
distinguish between dead and healthy cells, as when animal cells undergo programmed
cell death, or apoptosis. In this case, PS lipids that are normally found enriched in the
cytosolic leaflet, distribute between both leaflets of the bilayer. This functions as a
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