On the small size of liquid-disordered + liquid-ordered nanodomains.

Four-component phase diagrams reveal that Liquid-disordered + liquid-ordered (Ld + Lo) nanodomains are exclusively found adjacent to a three-phase region, and so cannot be a one-phase microemulsion. Of importance for understanding biological membranes, a small change in lipid bilayer composition can change the size of these coexisting phase domains hundreds of fold, between tens of nanometers and microns. Nanodomain diameter, measured from small angle neutron scattering, is in the range 15-35 nm, consistent with stabilization by repulsive dipole fields. Ld/Lo line tension controls the Ld + Lo domain size transition. Other than size, chemical and physical properties of the phase domains do not seem to change during the transition. Unfavorable lipid-lipid pairwise interactions, rather than phase thickness mismatch, seem to be the main reason for Ld + Lo immiscibility. Pairwise interactions of cholesterol-phospholipid seem to be favorable, whereas pairwise interactions of high-melting phospholipid with low-melting phospholipid are unfavorable. Measured Ld/Lo line tension, like the phase separation, is created mainly by unfavorable lipid-lipid pairwise interactions. Lipid dipole-dipole repulsion opposes these unfavorable lipid-lipid pairwise interactions and thus, in a sense, is the reason that nanodomains form. Bilayer physical and chemical properties measured from macroscopic domains of coexisting Ld + Lo phases should be good approximations for the properties of coexisting nanoscopic domains.