Flip-flop asymmetry of cholesterol in model membranes induced by thermal gradients.

Lipid asymmetry is a crucial property of biological membranes and significantly influences their physical and mechanical properties. It is responsible for maintaining different chemical environments onthe external and internal surfaces of cells and organelles and plays a vital role in many biologicalprocesses such as cell signalling and budding. In this work we show, using non-equilibrium moleculardynamics (NEMD) simulations, that thermal fields can induce lipid asymmetry in biological membranes. We focus our investigation on cholesterol, an abundant lipid in the plasma membrane, witha rapid flip-flop rate, significantly influencing membrane properties. We demonstrate that thermalfields induce membrane asymmetry with cholesterol showing thermophobic behaviour and thereforeaccumulating on the cold side of the membrane. This work highlights a possible experimental routeto preparing and controlling asymmetry in synthetic membranes.