Effect of cholesterol on the lactosylceramide domains in phospholipid bilayers
Effect of cholesterol on the lactosylceramide domains in phospholipid bilayers
复制标题
胆固醇对磷脂双层中乳糖神经酰胺结构域的影响
DOI：
10.1016/j.bpj.2022.02.037
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发表时间：
2022
影响因子：
3.4
通讯作者：
Murata Michio
中科院分区：
文献类型：
--
作者：
Hanashima Shinya;Ikeda Ryuji;Matsubara Yuki;Yasuda Tomokazu;Tsuchikawa Hiroshi;Slotte J. Peter;Murata Michio
免疫细胞质膜中的乳糖神经酰胺（LacCer）是一种重要的脂质，通过与胆固醇（Cho）一起形成富含LacCer的结构域，在先天免疫中发出信号。然而，在多组分膜中形成的LacCer结构域的性质仍然不清楚。在这项研究中，我们研究了性质的LacCer结构域中形成的含Cho的1-棕榈酰-2-油酰磷脂酰胆碱（POPC）膜的氘固态NMR和荧光寿命。已知LacCer-LacCer的强亲和力（亲同性相互作用）在单一LacCer双层中诱导热稳定的凝胶相。在LacCer/Cho二元膜中，Cho通过其有效的有序效应逐渐使LacCer凝胶相不稳定以形成液体有序相。在不含Cho的LacCer/POPC二元体系中，10′，10 ′-d2-LacCer和18′，18 ′，18 ′-d3-LacCer探针的~ 2 H NMR谱表明，LacCer与POPC在膜中的互溶性较差，形成稳定的凝胶相，没有分布在液晶区。LacCer/POPC膜的层状结构在约60°C下逐渐被破坏，而Cho的添加增加了层状结构的热稳定性。此外，在LacCer/POPC/Cho三元膜中，LacCer凝胶相的面积及其链序均减小，而在LacCer/Cho二元膜中观察到的液体有序结构域未观察到。Cho围绕LacCer凝胶结构域释放LacCer，并促进在LacCer/POPC/Cho膜的液晶结构域中形成亚微米至纳米尺度的小结构域，如由trans-parinaric acid和trans-parinaric acid-LacCer的荧光寿命所揭示的。我们的研究结果的LacCer结构域的膜特性，特别是在Cho的存在下，将有助于阐明生物膜中的LacCer结构域的特性。
Lactosylceramide (LacCer) in the plasma membranes of immune cells is an important lipid for signaling in innate immunity through the formation of LacCer-rich domains together with cholesterol (Cho). However, the properties of the LacCer domains formed in multicomponent membranes remain unclear. In this study, we examined the properties of the LacCer domains formed in Cho-containing 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) membranes by deuterium solid-state NMR and fluorescence lifetimes. The potent affinity of LacCer-LacCer (homophilic interaction) is known to induce a thermally stable gel phase in the unitary LacCer bilayer. In LacCer/Cho binary membranes, Cho gradually destabilized the LacCer gel phase to form the liquid-ordered phase by its potent order effect. In the LacCer/POPC binary systems without Cho, the2H NMR spectra of 10′,10′-d2-LacCer and 18′,18′,18′-d3-LacCer probes revealed that LacCer was poorly miscible with POPC in the membranes and formed stable gel phases without being distributed in the liquid crystalline domain. The lamellar structure of the LacCer/POPC membrane was gradually disrupted at around 60°C, whereas the addition of Cho increased the thermal stability of the lamellarity. Furthermore, the area of the LacCer gel phase and its chain order were decreased in the LacCer/POPC/Cho ternary membranes, whereas the liquid-ordered domain, which was observed in the LacCer/Cho binary membrane, was not observed. Cho surrounding the LacCer gel domain liberated LacCer and facilitated forming the submicron to nano-scale small domains in the liquid crystalline domain of the LacCer/POPC/Cho membranes, as revealed by the fluorescence lifetimes oftrans-parinaric acid andtrans-parinaric acid-LacCer. Our findings on the membrane properties of the LacCer domains, particularly in the presence of Cho, would help elucidate the properties of the LacCer domains in biological membranes.