Molecular ferries: membrane carriers that promote phospholipid flip-flop and chloride transport

The facilitated transport of ionic or polar solutes through biological membranes is an essential process for cellular life, and a major technical goal of the pharmaceutical industry. Synthetic receptors with affinities for anions are shown to act as molecular ferries and facilitate the movement of chloride ions and salts across vesicle and cell membranes. A process that competes with chloride transport is phospholipid translocation or flip-flop. This has led to the development of synthetic scramblases that can alter the transmembrane distribution of phospholipids and induce biological responses such as membrane enzyme activation. The facilitated translocation of phospholipids with multiply-charged head groups, like phosphatidylserine, is a difficult supramolecular challenge that requires a complementary, multitopic receptor with appropriate amphiphilicity.