Lipid Raft Formation: Key Role of Polyunsaturated Phospholipids

The forces that drive lipid raft formation are poorly understood. To date, most of the attention has focused on attractive interactions between cholesterol and high‐melting lipids. Remarkably little attention has been paid to repulsive forces. Here, we show that repulsive interactions between an exchangeable mimic of cholesterol and an exchangeable mimic of a low‐melting phospholipid in liquid‐disordered bilayers can be much stronger than the attractive forces between this same sterol and an exchangeable mimic of a high‐melting phospholipid in liquid‐ordered bilayers. We conclude that polyunsaturated phospholipids have been largely overlooked as major players in lipid raft formation. This knowledge should stimulate considerable interest in controlling the levels of polyunsaturated phospholipids for the proper functioning of cell membranes.