Many cellular lipid bilayers consist of leaflets that differ in their lipid composition - a non-equilibrium state actively maintained by cellular sorting processes that counter passive lipid flip-flop. While this lipidomic aspect of membrane asymmetry has been known for half a century, its elastic and thermodynamic ramifications have garnered attention only fairly recently. Notably, the torque arising when lipids of different spontaneous curvature reside in the two leaflets can be counterbalanced by a difference in lateral mechanical stress between them. Such membranes can be essentially flat in their relaxed state, despite being compositionally strongly asymmetric, but they harbor a surprisingly large but macroscopically invisible differential stress. This hidden stress can affect a wide range of other membrane properties, such as the resistance to bending, the nature of phase transitions in its leaflets, and the distribution of flippable species, most notably sterols. In this short note we offer a concise overview of our recently proposed basic framework for capturing the interplay between curvature, lateral stress, leaflet phase behavior, and cholesterol distribution in generally asymmetric membranes, and how its implied signatures might be used to learn more about the hidden but physically consequential differential stress.
