In our Martini 3 model, an effort was made to reach a compromise between overall hydrophobicity and miscibility within different lipid phases. This balance also reflects the complex structure of cholesterol, which shows both cyclic alkane and branched alkane character. The hydroxyl and double bond moieties are represented by Martini 3 P1 and C4 bead types, respectively. The sterol core (R2, R3 and R4) consists of C3 beads. These beads were parameterized to be used in cyclic alkanes, and are slightly less hydrophobic than C2 and C1 bead types while maintaining good miscibility with C1. The branched groups of the model -the protruding methyl groups and the aliphatic chain (R5, R6, C1 and C2) -consist of C2 beads. These were parameterized specifically to be used as branched alkanes. Indeed, the atomistic structures underlying these beads have a much higher hydrogen-to-carbon ratio than those of the sterol core. C2 beads have a higher interaction with C1 beads (which make up the Martini 3 saturated acyl chains) than their selfinteraction. These beads should increase cholesterol enrichment within saturated lipid phases, which coupled with entropic packing effects, should induce favorable lipid phase separation. Indeed, the strategy of using a slightly higher cross-interaction between C2-C1 is analogous to the non-bonded fix used in the parametrization of cholesterol in CHARMM force-field 101 . In Martini 2, this effect was included in the cross-interactions of the different bead sizes of lipid C1 tails and cholesterol SC1 beads.