Active regulation of intrinsic curvature by eukaryotic phospholipid metabolism

Membranes contain thousands of different lipids, but it is poorly understood why their compositions vary across cell types and environments. We report that lipid metabolism balances the molecular curvature of phospholipids, a parameter that describes their shape and propensity to destabilize flat sheets. We utilized extreme hydrostatic pressures-similar to those found in the deep ocean-to change the shape (reduce the curvature) of phospholipids in growing cells. Yeast and human cells respond to this stress by increasing synthesis of distinct high-curvature lipid species. The results support a model in which eukaryotic cells actively regulate lipid composition to maintain their membranes in a frustrated state, a dynamic that could be important for maintaining core functions in membrane trafficking.