Spatial arrangement and orientation of cholesterol affect cholesterol diffusivity in lipid membranes

The lateral diffusion and flip-flop of cholesterol are involved in multiple functions of lipid membranes such as the formation of cholesterol-enriched nanodomains. The subdiffusion of cholesterol, where its lateral mean square displacement scales with time t as 〈Δr²(t)〉 ∼ t^α with 0 < α < 1, spans up to several hundreds of nanoseconds. More interestingly, a recent study [1] reported that there were two regimes of subdiffusion with different exponents: the first regime with an exponent α₁ at a short time scale (~ 1 ns) and the second one with α₂ (0 < α₁ < α₂ < 1) at a longer time scale (~ 10² ns). The mechanism for such complicated cholesterol diffusion remains elusive. In this study, we employ coarse-grained molecular dynamics simulations to investigate the cholesterol transport in lipid membranes. We find that the cholesterol diffuses much faster when the cholesterol lies at the membrane center with horizontal orientation. On the other hand, the cholesterol diffusion is relatively slow when it stays at the leaflets. We also find that the center cholesterol undergoes subdiffusion at a short time scale (~ 1 ns), while leaflet cholesterol undergoes the subdiffusion at a longer timescale (~ 10² ns), which is consistent with previous studies.
[1] Phys. Rev. Lett., 109, 188103 (2012)