Non-Stereotypical Distribution and Effect of Ergosterol in Lipid Membranes

Sterols are an important class of lipids that regulate many biological processes. Among them, ergosterol in fungi and some protists is surprisingly understudied compared to cholesterol from animal membranes. Based on their similarity in chemical structure, ergosterol is assumed to modulate membrane in the similar fashion as cholesterol. In this study, however, we revealed very different interaction between ergosterol and lipid membranes. Using Neutron Membrane Diffraction, we found ergosterol is embedded much shallower than cholesterol in the bilayer. It doesn’t change the membrane thickness as much, indicating little condensation effect. From Neutron Spin Echo spectroscopy, we found ergosterol actually can both rigidify and soften membranes at different concentrations. The Quasi Elastic Neutron Scattering measurement of lateral lipid diffusion indicates that ergosterol promotes a jump diffusion of POPC, while cholesterol keeps the same continuous lateral diffusion mechanism as in the pure POPC membrane. All those results point to quite distinct interactions of ergosterol with membranes as compared to cholesterol. These structural and dynamical insights provide basic understandings for the properties of membranes containing ergosterol, as well as the implication for lipid rafts and drug interaction in those membranes.