Stability and liquid-liquid phase separation in mixed saturated lipid bilayers.

The phase stability of a fluid lipid bilayer composed of a mixture of DC(18)PC, (DSPC), and a shorter DCn(s) PC, with n(s) from 8 to 17, has been studied using a self-consistent field theory that explicitly includes molecular details and configurational properties of the lipid molecules. Phase separation between two liquid phases was found when there was a sufficient mismatch between the hydrophobic thicknesses of the two bilayers composed entirely of one component or the other. This occurs when n(s) <or = 12 and there is a sufficient concentration of the shorter lipid. The mixture separates into a thin bilayer depleted of DSPC and a thick bilayer enriched in DSPC. Even when there is no phase separation, as in the cases when there is either insufficient concentration of a sufficiently short lipid or any concentration of a lipid with n(s) > 12, we observe that the effect of the shorter lipid is to increase the susceptibility of the system to fluctuations in the concentration. This is of interest, given that a common motif for the anchoring of proteins to the plasma membrane is via a myristoyl chain, that is, one with 14 carbons.