How lipid asymmetry impacts ordered lipid domain (raft) formation may yield important clues to how ordered domain formation is regulated in vivo. Under some conditions, a sphingomyelin (SM) and cholesterol-rich ordered domain in one leaflet induces ordered domain formation in the corresponding region of an opposite leaflet composed of unsaturated phosphatidylcholine (PC) and cholesterol. In other conditions, the formation of ordered domains in a SM and cholesterol-rich leaflet can be suppressed by an opposite leaflet containing unsaturated PC and cholesterol. To explore how PC unsaturation influences the balance between these behaviors, domain formation was studied in asymmetric and symmetric lipid vesicles composed of egg SM, cholesterol, and either unsaturated dioleoyl PC (DOPC) or 1-palmitoyl 2-oleoyl PC (POPC). The temperature dependence of ordered domain formation was measured using Förster resonance energy transfer, which detects nanodomains as well as large domains. In cholesterol-containing asymmetric SM+PC outside/PC inside vesicles, the PC-containing inner leaflet tended to destabilize ordered domain formation in the SM+PC-containing outer leaflet relative to ordered domain stability in cholesterol-containing symmetric SM/PC vesicles. Residual ordered domain formation was detected in cholesterol-containing asymmetric SM+DOPC outside/DOPC inside vesicles, but ordered domain formation was completely or almost completely suppressed by asymmetry in cholesterol-containing SM+POPC outside/POPC inside vesicles over the entire temperature range measured. Suppression of ordered domain formation in the latter vesicles was confirmed by fluorescence anisotropy measurements. Because mixtures of SM, POPC, and cholesterol form domains in symmetric vesicles, and this lipid composition mimics plasma membranes to a significant degree, it is possible that under some conditions in vivo the loss of lipid asymmetry could trigger ordered domain formation.

中文翻译：

---

通过脂质不对称性的丧失诱导有序的脂质结构域（筏）形成

脂质不对称如何影响有序脂质结构域（筏）的形成可能会产生关于有序结构域形成如何在体内调节的重要线索。在某些情况下，一个小叶中的鞘磷脂 (SM) 和富含胆固醇的有序结构域会在由不饱和磷脂酰胆碱 (PC) 和胆固醇组成的相对小叶的相应区域中诱导有序结构域的形成。在其他情况下，SM 和富含胆固醇的小叶中有序结构域的形成可以被含有不饱和 PC 和胆固醇的相反小叶抑制。为了探索 PC 不饱和度如何影响这些行为之间的平衡，在由鸡蛋 SM、胆固醇和不饱和二油酰 PC (DOPC) 或 1-棕榈酰 2-油酰 PC (POPC) 组成的不对称和对称脂质囊泡中研究了结构域形成。使用 Förster 共振能量转移测量有序域形成的温度依赖性，它检测纳米域以及大域。在含有胆固醇的不对称 SM+PC 外部/PC 内部囊泡中，相对于含胆固醇对称 SM/PC 囊泡中有序结构域的稳定性，含有 PC 的内小叶倾向于破坏含 SM+PC 外小叶中有序结构域的形成。在囊泡内含胆固醇的不对称 SM+DOPC/DOPC 内检测到残留有序结构域形成，但在整个测量温度范围内，囊泡内含胆固醇 SM+POPC/POPC 内的不对称性完全或几乎完全抑制有序结构域形成. 荧光各向异性测量证实了后者囊泡中有序结构域形成的抑制。由于 SM、POPC 和胆固醇的混合物在对称囊泡中形成结构域，并且这种脂质成分在很大程度上模拟质膜，因此在体内某些条件下，脂质不对称性的丧失可能会触发有序结构域的形成。