Phase separation in bilayer lipid membranes: Effects on the inner leaf due to coupling to the outer leaf

The combined effects of the tendency of cholesterol to order lipids in the liquid phase and the coupling between lipids in the two leaves of a bilayer are investigated theoretically utilizing a Landau free energy. We show that as a consequence of these combined effects, lateral phase separation in the outer leaf between cholesterol-rich and -poor liquids causes a similar, but weaker, phase separation in the inner leaf. Just as the areal density of lipids in the outer leaf increases in the cholesterol-rich regions, so the areal density of lipids also increases in the inner leaf. Thus, the areal density in the inner leaf varies spatially, reflecting spatial variations of the areal density in the outer leaf. This provides a mechanism for proteins attached to the inner leaf via a hydrocarbon tether to respond to variations in the composition of the outer leaf. We also note that the effect of coupling between the leaves should be observable in artificial bilayers.