How cholesterol could be drawn to the cytoplasmic leaf of the plasma membrane by phosphatidylethanolamine

TL;DR

This paper proposes a mechanism by which cholesterol is attracted to the cytoplasmic leaf of the plasma membrane, driven by the presence of phosphatidylethanolamine, and models its distribution accordingly.

Contribution

It introduces a model explaining cholesterol distribution influenced by phosphatidylethanolamine's effects on membrane bending energy.

Findings

50-60% of cholesterol in the inner leaf of human erythrocytes

Cholesterol distribution explained by membrane bending energy considerations

Mechanism involving PE's effect on membrane curvature

Abstract

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.