BPS2026 – Toward decoding and engineering membrane functions

The cell membrane is a responsive interface and selective barrier that organizes and protects life. Lipids, the amphiphilic molecules forming the bilayer, are central to this function. Yet we do not know why cells tightly regulate the synthesis of hundreds of distinct lipids when a single lipid suffices to form a bilayer. What is all that complexity good for? What role did it play in the origin and evolution of cells? And can we harness lipid diversity to engineer membranes for synthetic life? The combination of lipids in a membrane defines its physical properties, which shape membrane function and cellular fitness. Thus, while one lipid can form a bilayer, multiple lipids are needed to optimize membranes to physiological and environmental demands. To explore these principles, we have established genomically minimal bacterial systems—pathogenic Mycoplasma and the minimal cell (JCVI-syn3B)—as modifiable membrane platforms. By tuning and minimizing their lipidomes, we showed that just two lipids are sufficient, though far from optimal, for sustaining life. These systems now allow us to reintroduce genomic and chemical complexity in a controlled way, uncovering the essential components of a functional membrane. Our long-term vision is to understand how membrane material properties are genomically encoded—so that we can retrace their evolutionary origins and design programmable membranes for synthetic life.