Composition dependence of cholesterol flip-flop rates in physiological mixtures

Unbiased, all-atom simulations of mixtures representative of the inner and outer leaflets of a mammalian red blood cell and a synaptic vesicle reveal many cholesterol flip-flop events over the 5 μsec duration of the simulations. Enough events are observed for a direct estimate of the flip-flop rate. Slower rates are found in more ordered membranes, and faster rates in more disordered membranes, consistent with earlier reports in the literature. However, the rates found here are neither as fast as the fastest nor as slow as the slowest rates obtained by previous simulations. The difference likely stems from the compositions studied here, which unlike previous work include exclusively lipids with differing acyl chains, as observed in mammalian lipidomes.