Interleaflet Coupling and Domain Registry in Phase-Separated Lipid Bilayers  G. Garbès Putzel, Mark J. Uline, Igal Szleifer, M. Schick  Biophysical Journal  Volume 100, Issue 4, Pages 996-1004 (February 2011) DOI: 10.1016/j.bpj.2011.01.021 Copyright © 2011 Biophysical Society Terms and Conditions

Figure 1 (Left) Phase separation in a symmetric lipid bilayer in which the domains in the two leaflets are aligned. (Right) If the domains are displaced out of alignment, mismatch regions of asymmetric composition (gray) are created at the expense of the areas of the symmetric coexisting phases. Biophysical Journal 2011 100, 996-1004DOI: (10.1016/j.bpj.2011.01.021) Copyright © 2011 Biophysical Society Terms and Conditions

Figure 2 Interleaflet domain registry in a phase-separated symmetric lipid bilayer. The boundary between the lo and ld phase regions is shown as a solid line in the upper leaflet and as a dashed line in the lower leaflet. The characteristic width of the mismatch region is denoted as ξ⊥. Biophysical Journal 2011 100, 996-1004DOI: (10.1016/j.bpj.2011.01.021) Copyright © 2011 Biophysical Society Terms and Conditions

Figure 3 (Top) Initial configuration of the mismatch process. There are equal areas, A, of symmetric ld and lo bilayer. (Bottom) Final configuration of the mismatch process. The upper leaflet has the same composition as it has in the the ld phase, whereas the lower leaflet has the composition as it has in the lo phase. The total area is 2A′. Biophysical Journal 2011 100, 996-1004DOI: (10.1016/j.bpj.2011.01.021) Copyright © 2011 Biophysical Society Terms and Conditions

Figure 4 Phase diagram of the model bilayer consisting of identical leaves of cholesterol (C), dipalmitoylphophatidylcholine (S), and dioleoylphosphatidylcholine (U) at a temperature of T = 17°C. Four tie lines between lo and ld phases are labeled A–D. Biophysical Journal 2011 100, 996-1004DOI: (10.1016/j.bpj.2011.01.021) Copyright © 2011 Biophysical Society Terms and Conditions

Figure 5 Typical configuration of a segment of the interface between the lo and ld phases (see also Fig. 2. The interface boundaries in the upper and lower leaflets are described by the functions y1(x) and y2(x), respectively. The area of mismatch where the two leaflets have different compositions is shaded. Biophysical Journal 2011 100, 996-1004DOI: (10.1016/j.bpj.2011.01.021) Copyright © 2011 Biophysical Society Terms and Conditions

Figure 6 Typical configuration in lattice Monte Carlo simulation of two coupled mixtures, representing the two leaflets of a phase-separating bilayer. The states of the different lattice sites are color-coded: black, liquid-ordered in both leaflets; white, ld in both leaflets; dark gray, lo in the upper leaflet and ld in the lower leaflet; light gray, ld in the upper leaflet and lo in the lower leaflet. Details of the simulation are given in the Supporting Material. Biophysical Journal 2011 100, 996-1004DOI: (10.1016/j.bpj.2011.01.021) Copyright © 2011 Biophysical Society Terms and Conditions

Figure 7 Solid line graphs −ln[P(a)], where P(a) is obtained from a histogram of the areas of mismatch regions (Fig. 6, light and dark gray) in lattice Monte Carlo simulations of two coupled mixtures undergoing phase separation. The dashed line is for each bin in the histograms of mismatch areas, the fraction of lattice sites, among those belonging to mismatch regions, which also lie on the boundaries of those regions. The dash-dotted line is a linear fit to −ln[P(a)] based on mismatch areas that are insufficiently large, as shown by the fact that the perimeter/area ratio is still nonnegligible. Biophysical Journal 2011 100, 996-1004DOI: (10.1016/j.bpj.2011.01.021) Copyright © 2011 Biophysical Society Terms and Conditions