The segregation of lipids into lateral membrane domains has been extensively studied. It is well established that the structural differences between phospholipids play an important role in lateral membrane organization. When a high enough cholesterol concentration is present in the bilayer, liquid-ordered (Lo) domains, which are enriched in cholesterol and saturated phospholipids such as sphingomyelin (SM), may form. We have recently shown that such a formation of domains can be facilitated by the affinity differences of cholesterol for the saturated and unsaturated phospholipids present in the bilayer. In mammalian membranes, the saturated phospholipids are usually SMs with different acyl chains, the abundance of which vary with cell type. In this study, we investigated how the acyl chain structure of SMs affects the formation of SM- and cholesterol-enriched domains. From the analysis of trans-parinaric acid fluorescence emission lifetimes, we could determine that cholesterol facilitated lateral segregation most with the SMs that had 16 carbon-long acyl chains. Using differential scanning calorimetry and Förster resonance energy transfer techniques, we observed that the SM- and cholesterol-enriched domains with 16 carbon-long SMs were most thermally stabilized by cholesterol. The Förster resonance energy transfer technique also suggested that the same SMs also form the largest Lo domains. In agreement with our previously published data, the extent of influence that cholesterol had on the propensity of lateral segregation and the properties of Lo domains correlated with the relative affinity of cholesterol for the phospholipids present in the bilayers. Therefore, the specific SM species present in the membranes, together with unsaturated phospholipids and cholesterol, can be used by the cell to fine-tune the lateral structure of the membranes.

中文翻译：

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鞘磷脂酰基链影响鞘磷脂和胆固醇富集域的形成

脂质分离成侧膜结构域已被广泛研究。众所周知，磷脂之间的结构差异在侧膜组织中起着重要作用。当双层中存在足够高的胆固醇浓度时，可以形成富含胆固醇和饱和磷脂如鞘磷脂 (SM) 的液体有序 (Lo) 域。我们最近表明，这种结构域的形成可以通过胆固醇对双层中存在的饱和和不饱和磷脂的亲和力差异来促进。在哺乳动物细胞膜中，饱和磷脂通常是具有不同酰基链的 SM，其丰度因细胞类型而异。在这项研究中，我们研究了 SM 的酰基链结构如何影响富含 SM 和胆固醇的结构域的形成。从反式肝素酸荧光发射寿命的分析中，我们可以确定胆固醇最有助于具有 16 个碳长酰基链的 SM 的横向分离。使用差示扫描量热法和 Förster 共振能量转移技术，我们观察到具有 16 个碳长 SM 的富含 SM 和胆固醇的域最受胆固醇热稳定。Förster 共振能量转移技术还表明相同的 SM 也形成了最大的 Lo 域。与我们之前公布的数据一致，胆固醇对横向分离倾向的影响程度和 Lo 结构域的特性与胆固醇对双层中存在的磷脂的相对亲和力相关。因此，细胞膜中存在的特定 SM 物种，连同不饱和磷脂和胆固醇，可以被细胞用来微调膜的横向结构。