Sterols have been ascribed a major role in URLanization of biological membranes, in particular for the formation of liquid ordered domains in complex lipid mixtures. Interestingly, evolution has resulted in a preference for chemically similar but distinct sterol types - with cholesterol the major sterol of mammalian cells and ergosterol dominating in membranes of fungal cells. However, the molecular basis and functional consequences of the choice in sterols are not well understood. Here, we employed molecular dynamics simulations to compare the effects of cholesterol and ergosterol  on binary mixtures with saturated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipids. Our simulations with varying sterol concentrations and temperatures revealed that while both sterols were able to induce the formation of liquid ordered membrane domains, cholesterol had a noticeably stronger impact on lipids condensing and ordering . The observed differences could be attributed to the higher planarity of the cholesterol ring region. This planarity combined with an inherent asymmetry in its molecular interactions led to better alignment and hence stronger interaction with saturated acyl chains. Our results show that ergosterol does not have an increased capacity to form ordered lipid domains compared to cholesterol and indicate that the high order demonstrated for  fungal plasma membranes must therefore be generated via different mechanisms.
Sterols have been ascribed a major role in URLanization of biological membranes, in particular for the formation of liquid ordered domains in complex lipid mixtures. Here, we employed molecular dynamics simulations to compare the effects of cholesterol and ergosterol as the major sterol of mammalian and fungal cells, respectively, on binary mixtures with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as a proxy for saturated lipids. In agreement with previous work, we observe that the addition of sterol molecules modifies the order of DPPC both in the gel phase and in the liquid phase. When disentangling systematic and random properties of the order parameter distribution, related to the tilt angle and the fluctuations, respectively, a more detailed picture of the impact of sterols can be formulated, revealing, e.g., an approximate temperature-concentration superposition ranging from the liquid to the gel phase. Furthermore, a new quantitative measure to identify the presence of collective sterol effects is discussed. Moreover, when comparing both types of sterols, addition of cholesterol has a noticeably stronger impact on phospholipid properties than of ergosterol . The observed differences can be attributed to higher planarity of the cholesterol ring region. This planarity combined with an inherent asymmetry in its molecular interactions leads to better alignment and hence stronger interaction with saturated acyl chains. Our results suggest that the high order demonstrated for ergosterol in fungal plasma membranes must therefore be generated via additional mechanisms.
D
Interestingly, evolution has resulted in a preference for chemically similar but distinct sterol types - with cholesterol the major sterol of mammalian cells and ergosterol dominating in membranes of fungal cells. However, the molecular basis and functional consequences of the choice in sterols are not well understood.
A
as the major sterol of mammalian and fungal cells, respectively,
D
saturated
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lipids. Our simulations with varying sterol concentrations and temperatures revealed that while both sterols were able to induce the formation of liquid ordered membrane domains, cholesterol had
as a proxy for saturated lipids. In agreement with previous work, we observe that the addition of sterol molecules modifies the order of DPPC both in the gel phase and in the liquid phase. When disentangling systematic and random properties of the order parameter distribution, related to the tilt angle and the fluctuations, respectively, a more detailed picture of the impact of sterols can be formulated, revealing, e.g., an approximate temperature-concentration superposition ranging from the liquid to the gel phase. Furthermore, a new quantitative measure to identify the presence of collective sterol effects is discussed. Moreover, when comparing both types of sterols, addition of cholesterol has
R
lipids condensing and ordering
phospholipid properties than of ergosterol
R
could
can
D
the
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led
leads
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show that ergosterol does not have an increased capacity to form ordered lipid domains compared to cholesterol and indicate that
suggest that
A
ergosterol in
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different
additional