Researchers have developed a way to chemically remodel synthetic cell membranes, similar to the way enzymes remodel mammalian cell membranes in living cells. In biological cells, the remodeling of membrane phospholipids by enzymes such as acyltransferases and transacylases plays a key role in many cell functions, such as division, membrane transport, and cell signaling. Synthetic membranes have been developed as stand-ins for studying these processes in native membranes, but researchers have not been able to mimic membrane remodeling. Neal K. Devaraj and coworkers at the University of California, San Diego, now report the use of chemical reactions to remodel phospholipids in synthetic membranes (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1605541113). Each phospholipid contains a head group and a lipid acyl chain. The researchers reported earlier that native chemical ligation can combine head groups and lipid chains to create new phospholipids that assemble into synthetic membranes. They now show that reversible native chemical ligation can modify the head groups and lipid acyl chains of phospholipids already in artificial membranes. They also demonstrate that chemical phospholipid remodeling can influence membrane properties such as curvature and the ability to recruit proteins. The technique could make it easier to “understand the various roles of lipid remodeling in biological membranes,” Devaraj says.