Despite longstanding excitement and progress toward understanding liquid–liquid phase separation in natural and artificial membranes, fundamental questions have persisted about which molecules are required for this phenomenon. Except in extraordinary circumstances, the smallest number of components that has produced large-scale, liquid–liquid phase separation in bilayers has stubbornly remained at three: a sterol, a phospholipid with ordered chains, and a phospholipid with disordered chains. This requirement of three components is puzzling because only two components are required for liquid–liquid phase separation in lipid monolayers, which resemble half of a bilayer. Inspired by reports that sterols interact closely with lipids with ordered chains, we tested whether phase separation would occur in bilayers in which a sterol and lipid were replaced by a single, joined sterol–lipid. By evaluating a panel of sterol–lipids, some of which are present in bacteria, we found a minimal bilayer of only two components (PChemsPC and diPhyPC) that robustly demixes into micron-scale, liquid phases. It suggests an additional role for sterol–lipids in nature, and it reveals a membrane in which tie-lines (and, therefore, the lipid composition of each phase) are straightforward to determine and will be consistent across multiple laboratories.

中文翻译：

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甾醇-脂质能够在仅由两种组分组成的双层膜中实现大规模液-液相分离


尽管长期以来人们对天然膜和人造膜中的液-液相分离的理解一直令人兴奋并取得进展，但关于这种现象需要哪些分子的基本问题仍然存在。除特殊情况外，在双层中产生大规模液-液相分离的最少组分数量顽固地保持在三种：甾醇、具有有序链的磷脂和具有无序链的磷脂。这种对三种组分的要求令人费解，因为脂质单层中的液-液相分离只需要两种组分，类似于双层的一半。受到甾醇与具有有序链的脂质密切相互作用的报道的启发，我们测试了在甾醇和脂质被单个连接的甾醇-脂质取代的双层中是否会发生相分离。通过评估一组甾醇脂质（其中一些存在于细菌中），我们发现只有两种成分（PChemsPC 和 diPhyPC）的最小双层，可以牢固地分层混合成微米级液相。它表明甾醇脂质在自然界中具有额外的作用，并且它揭示了一种膜，其中的连接线（以及因此每个相的脂质成分）很容易确定，并且在多个实验室中是一致的。