Maximum Solubilities of Ergosterol and Stigmasterol in Various Lipid Membranes

The chemical structure of cholesterol is very similar to that of other sterols, such as bacteria sterol ergosterol and plant sterol stigmasterol. However, mammalian cells universally utilize cholesterol. Scientists have been wondering what makes cholesterol so unique that animal cells prefer cholesterol, not other sterols.  We recently measured the maximum solubilities of ergosterol and stigmasterol in various types of lipid membranes (DPPC, DOPC, POPC) using an anti-correlation light scattering technique. We found that cholesterol has the highest solubility in lipid membranes (~67 mole %) regardless the saturation of lipids, while other sterols have much lower solubilities.  Furthermore, ergosterol and stigmasterol have lower solubilities (15% - 22%) in unsaturated (DOPC) lipid bilayers and higher solubilities (40% - 55%) in saturated (DPPC) lipid bilayers. Our result shows that a small difference in sterol structure can result in a major difference in the behavior of sterols.  The uniquely high solubility of cholesterol is essential for cholesterol to perform its biological functions in mammalian cells.