17Cells, from microbes to man, adapt their membranes in response to the environment to maintain 18 functionality. How cells sense environmental change/stimuli and adapt their membrane accordingly 19 is unclear. In particular, how lipid composition changes and what lipid structural features are 20 necessary for homeostatic adaptation remains relatively undefined. Here, we examine the simple yet 21 adaptive lipidome of the plant-associated Gram-negative bacterium Methylobacterium extorquens 22 over a range of chemical and physical conditions. Using shotgun lipidomics, we explored adaptivity 23 over varying temperature, hyperosmotic and detergent stress, carbon sources, and cell density. 24Globally, we observed that as few as 10 lipids, representing ca. 30% of the lipidome, characterized 25 by 9 structural features account for 90% of the total changes. We revealed that variations in lipid 26 structural features are not monotonic over a given range of conditions (e.g. temperature) and are not 27 evenly distributed across lipid classes. Thus, despite the compositional simplicity of this lipidome, 28 the patterns in lipidomic remodeling suggest a highly adaptive mechanism with many degrees of 29 freedom. Our observations reveal constraints on the minimal lipidomic requirements for an adaptive 30 membrane and provide a resource for unraveling the design principles of living membranes. 31Puth, K., Hofbauer, H.F., Sáenz, J.P., and Ernst, R. (2015). Homeostatic control of biological 595 membranes by dedicated lipid and membrane packing sensors. Biol Chem 396, 1043-1058. 596