In contrast to the original cholesterol model, we observed only small temperature differences between the two phospholipid types with the optimized model. Even for a low lincs order=4 and long time step of 30 fs, the temperature difference is only 3.9 K (Fig- ure 3a). For lincs order=6 and a 30 fs time steps, ∆T drops to 0.2 K. Moreover, the temperature difference between the two membrane domains was in all cases under 8 K and became negligible for time steps below 30 fs or lincs order=8 for a 30-fs time step. Both models converge to the same values at small ∆T , further supporting the consistency of our optimization procedure.