Sterol structure and sphingomyelin acyl chain length modulate lateral packing elasticity and detergent solubility in model membranes
Sterol structure and sphingomyelin acyl chain length modulate lateral packing elasticity and detergent solubility in model membranes
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DOI：
10.1016/s0006-3495(03)74794-8
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发表时间：
2003-12-01
影响因子：
3.4
通讯作者：
Brown, RE
中科院分区：
文献类型：
--
作者：
Li, XM;Momsen, MM;Brown, RE
膜微区，如小窝和筏，富含胆固醇和鞘磷脂，显示液体有序相特性，并作为蛋白质组织平台。本研究的目的是确定甾醇和鞘磷脂的结构特征，调节表面压缩和溶解洗涤剂，因为液体有序相显示低的横向弹性和耐溶解Triton X-100。与胆固醇相比，甾醇结构的变化涉及改变极性头基（例如，6-酮基胆甾烷醇）或消除异辛基烃尾部（例如，5-雄甾烯-3 β-醇）。鞘磷脂的合成变化导致不同长度但具有生物相关性的均质酰基链。使用朗缪尔表面天平，在各种表面压力下评估表面压缩模量（C-s（-1）），包括模拟生物膜条件的那些（pi大于或等于30 mN/m）。鞘磷脂-甾醇混合物一般弹性较小，在横向意义上比链匹配的磷脂酰胆碱-甾醇混合物在同等的高甾醇摩尔分数。增加鞘磷脂中6-酮基胆甾烷醇或5-雄甾烯-3 β-醇的含量会降低横向弹性，但效果远低于胆固醇。我们的研究结果表明，胆固醇是理想的结构，最大限度地减少膜鞘脂的横向弹性，使耐曲拉通X-100增溶，并与鞘磷脂，含有饱和的酰基链长度相似的鞘氨醇碱相互作用。
Membrane microdomains, such as caveolae and rafts, are enriched in cholesterol and sphingomyelin, display liquid-ordered phase properties, and putatively function as protein organizing platforms. The goal of this investigation was to identify sterol and sphingomyelin structural features that modulate surface compression and solubilization by detergent because liquid-ordered phase displays low lateral elasticity and resists solubilization by Triton X-100. Compared to cholesterol, sterol structural changes involved either altering the polar headgroup (e.g., 6-ketocholestanol) or eliminating the isooctyl hydrocarbon tail (e.g., 5-androsten-3beta-ol). Synthetic changes to sphingomyelin resulted in homogeneous acyl chains of differing length but of biological relevance. Using a Langmuir surface balance, surface compressional moduli (C-s(-1)) were assessed at various surface pressures including those (pi greater than or equal to 30 mN/m) that mimic biomembrane conditions. Sphingomyelin-sterol mixtures generally were less elastic in a lateral sense than chain-matched phosphatidylcholine-sterol mixtures at equivalent high sterol mole fractions. Increasing content of 6-ketocholestanol or 5-androsten-3beta-ol in sphingomyelin decreased lateral elasticity but much less effectively than cholesterol. Our results indicate that cholesterol is ideally structured for maximally reducing the lateral elasticity of membrane sphingolipids, for enabling resistance to Triton X-100 solubilization, and for interacting with sphingomyelins that contain saturated acyl chains similar in length to their sphingoid bases.