Flip-Flop Promotion Mechanisms by Model Transmembrane Peptides

Lipid transbilayer movement (flip-flop) is regulated by membrane proteins that are involved in homeostasis and signaling in eukaryotic cells. In the plasma membrane, an asymmetric lipid composition is maintained by energy-dependent unidirectional transport. Energy-independent flip-flop promotion by phospholipid scramblases disrupts the asymmetry in several physiological processes, such as apoptosis and blood coagulation. In the endoplasmic reticulum, rapid flip-flop is essential for bilayer integrity because phospholipids are synthesized only in the cytoplasmic leaflet. Phospholipid scramblases are also involved in lipoprotein biogenesis, autophagosome formation, and viral infection. Although several scramblases have been identified and investigated, the precise flip-flop promotion mechanisms are not fully understood. Model transmembrane peptides are valuable tools for investigating the general effects of lipid-peptide interactions. We focus on the development of model transmembrane peptides with flip-flop promotion abilities and their mechanisms.