The interaction between metal cations, particularly biologically relevant ones like Ca and Mg 2+ , and lipids play a crucial role in the structure and function of biological membranes. Phosphatidylserine (PS), the most abundant negatively charged lipid in mammalian cell membranes, has been a focal point in studies of cation-lipid interactions. Research has shown that Ca 2+ and/or Mg 2+ can promote vesicle fusion 117 , induce aggregation and phase separation or even phase transitions 120 in PScontaining membranes. While PS has been extensively studied, similar behaviors have been noted in other anionic lipids, such as phosphoinositides 117, 121, 122 , phosphatidylglycerol , and phosphatidic acid . Here, we tested the capabilities of the new Martini 3 lipid models to successfully reproduce some of these cation-induced phenomena, focusing on the Ca 2+ -induced aggregation and resulting phase change behavior of PS.