Figure 2.

Increasing hydrophobic mismatch leads to two-step kinetics, but a registered equilibrium state is always reached. The equilibrium separated phases appear purer for stronger hydrophobic mismatch. (A) Images mapping evolution of the local lipid compositions in both leaflets for the DLPC (3:0 PC) mixture. There are four categories of transbilayer arrangements: both leaflets saturated (SS, red), both unsaturated (UU, blue) and asymmetric arrangements (SU, pink or US, light blue). The hydrophobic mismatch is small and the bilayer separates directly into registered ordered and disordered phases. The images on the far right show how the area of each local arrangement varies with time. Also shown are the corresponding distributions of the thickness of the bilayer, showing a final thickness difference of 0.4 nm between the registered ordered and disordered phases. (B) Increasing the tail length of the saturated lipid by one bead (DPPC) leads to a larger hydrophobic mismatch between the disordered and ordered phases. There is a small initial increase in the area of antiregistration (SU and US) until t ≃ 0.05 μs. (C) Increasing the number of beads in each tail of the saturated lipid to five (DAPC) further increases the degree of hydrophobic mismatch, leading to a final thickness difference of 1.7 nm between the registered ordered and disordered phases. Initial demixing is dominated by antiregistered domains causing an increase in the area of SU and US up to t ≃ 1.1 μs, after which registration takes over to complete the two-step kinetics. As expected, the bilayer thickness of the antiregistered phases is intermediate between the registered ordered and disordered phases. Repeat simulations with different initial conditions appear in the Supporting Information.