We also tested the impact of cholesterol on phase separation. We started by probing two specific conditions of the DPPC:CHOL binary phase diagram at 300 K. At 15 mol% cholesterol, DPPC bilayers remain fully in a gel phase, with the cholesterol molecules frozen within the hexagonal gel matrix (Supplementary Figure ). At 30 mol%, cholesterol can fluidify the gel matrix into an Lo phase where we observe the transient formation of small gel-like DPPC domains. Coexistence with these small domains is quite dynamic, with the gel domains assembling and then quickly dissolving after a few nanoseconds (Supplementary Video S1). Whether these transient gel-like domains are nucleation points for the formation of a larger gel-phase or gel-like substructure elements of the Lo phase that may exist at this temperature , this observation is already a promising improvement over Martini 2 which struggled to show any such structures . Experimental DPPC:CHOL binary phase studies conducted at 295-300 K 116-122 predict the gel to Lo/Gel transition to occur anywhere between 3 to 20 mol% cholesterol, with the following Lo/Gel to Lo transition occurring between 20 and 30 mol% cholesterol. The uncertainty in defining the transition boundaries is likely due to the intrinsic resolution and sensitivity limitations of the experimental methods used in probing these dynamic local domains in a membrane environment 122 . Nonetheless, our results reasonably match experimental observations. Note that given the nature of the 4-to-1 mapping of the Martini acyl chain beads, the Martini 3 DPPC represents both (16:0)2 and (18:0)2 PC lipids (i.e. DPPC and DSPC).