Rapid diffusion of cholesterol along polyunsaturated membranes via deep dives.

Cholesterol regulates the function of membrane proteins either via direct or membrane-mediated effects. Therefore, its ready availability is crucial for many protein-governed cellular processes. Recent studies suggest that cholesterol can partition to the core of polyunsaturated membranes, where cholesterol binding sites of many membrane proteins are also located. This core region is characterized by a lower viscosity. Therefore, we hypothesized that cholesterol partitioning into the membrane interior increases the rate of its diffusion in polyunsaturated membrane environments. We studied the behavior of cholesterol in membranes with increasing level of lipid chain unsaturation using a combination of atomistic and coarse-grained molecular dynamics simulations. Our simulations suggest a strong correlation between entropy-driven enhanced cholesterol partitioning to the membrane core and its faster lateral diffusion, which indicates that the less viscous membrane core indeed provides an efficient means for cholesterol movement in polyunsaturated membrane environments.