Experimental studies have found that both MC3 and KC2 form an inverse hexagonal phase at low pH with a hydration of around 7-12 water molecules per lipid. They also propose that the core of LNPs consists of around 75 mol% IL and 25 mol% cholesterol. The presence of cholesterol has previously been suggested to help maintain the inverted hexagonal phase of the LNPs based on atomistic MD simulations . The tests for formation of inverse hexagonal phase were therefore performed with KC2 and MC3 in the presence of either DSPC or cholesterol. Double bilayer systems were constructed of both MC3 (DUM3/DUMP) and KC2 (DUK2/DUKP) with 10 mol% DSPC or with 25 mol% cholesterol and low hydration (around 7 water molecules per lipid) and neutralizing ions, representing low and high pH, assuming fully charged or neutral lipids, based on the experimental conditions in the work by Philipp et al. . Indeed, both MC3 and KC2 form the inverse hexagonal phase in with both DSPC and cholesterol, however only at low pH, assuming a plus one charge for all the ILs. The inverse hexagonal phase does however not seem to depend on the presence or absence of either DSPC nor cholesterol, see Figure and. An additional test was performed with only MC3 and KC2 at low pH, and in fact the inverse hexagonal phase was formed as well. The simulations reach the same conclusion as obtained experimentally , that the phase is determined by the ionizable lipid and not the helper lipid DSPC nor cholesterol.