  In the mammalian plasma membrane, cholesterol can translocate rapidly between
the exoplasmic and cytoplasmic leaves, so that its distribution between them
should be given by the equality of its chemical potential in the leaves. Due to
its favorable interaction with sphingomyelin, which is almost entirely in the
outer leaf, one expects the great majority of cholesterol to be there also.
Experimental results do not support this, implying that there is some mechanism
which attracts cholesterol to the inner leaf. We hypothesize that it is drawn
there to reduce the bending free energy of the membrane caused by the presence
of phosphatidylethanolamine (PE). It does this in two ways: first by simply
diluting the amount of PE in the inner leaf, and second by ordering the tails
of the PE so as to reduce its spontaneous curvature. Incorporating this
mechanism into a model free energy for the bilayer, we find that between 50 and
60% of the total cholesterol should be in the inner leaf of human erythrocytes.
