Ergosterol has No Condensing Effect of Cholesterol

Abstract

Cholesterol is known for its condensing effect on phospholipids, which was first discovered in monolayers (Leathes, 1925), i.e., a binary mixture of a phospholipid and cholesterol have an average molecular area less than the sum of the molecular areas of the two components. The corresponding effect in bilayers where the thickness of the mixture is greater than that of each component alone is also well-known (Levine and Wilkins, 1971). At the maximum solubility, cholesterol can increase the thickness of DOPC by 5.1 A, SOPC by 5.8 A, POPC by 6.4 A and DMPC by 7.4 A (Hung et al. 2007). In fact cholesterol was called a membrane thickness buffer. Indeed it has been shown that the cholesterol-containing phospholipid bilayers maintain unvarying electron density profiles over a wide range of high relative humidity (Hung et al., 2007), whereas the profiles of pure phospholipid bilayers vary significantly within this range of RH. The modulation of membrane thickness by cholesterol is considered important for hydrophobic matching with membrane proteins in cell membranes. Due to the structural similarities, other sterols, such as ergosterol, are often believed to have the same universal effect on membrane properties as cholesterol, albeit to different degrees. We have measured the effect of ergosterol on the thickness of DOPC, POPC and DMPC as a function of sterol concentration. We found that not only the effect is much smaller than the effect of cholesterol (all changes are within 2 A), but in DOPC and POPC the effect is negative—it makes the membranes thinner, opposite to the effect of cholesterol. Also, ergosterol is not a membrane thickness buffer. The ergosterol-containing phospholipid bilayers have their electron density profiles varying with relative humidity. Thus it appears that ergosterol does not have the condensing effect of cholesterol.