Phospholipid transbilayer movement (flip-flop) in the plasma membrane is regulated by membrane proteins to maintain cell homeostasis and interact with other cells. The promotion of flip-flop by phospholipid scramblases causes the loss of membrane lipid asymmetry, which is involved in apoptosis, blood coagulation, and viral infection. Therefore, compounds that can artificially control flip-flop in the plasma membrane are of biological and medical interest. Here, we have developed lipid scrambling transmembrane peptides that can be inserted into the membrane. Time-resolved small-angle neutron scattering measurements revealed that the addition of peptides containing a glutamine residue at the center of the hydrophobic sequence to lipid vesicles induces the flip-flop of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. Peptides without the glutamine residue had no effect on the flip-flop. Because the glutamine-containing peptides exhibited scramblase activity in monomeric form, the polar glutamine residue would be exposed to the hydrocarbon region of the membrane, perturbing the membrane and promoting the lipid flip-flop. These scrambling peptides would be valuable tools to regulate lipid flip-flop in the plasma membrane.

中文翻译：

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膜可插入脂质加扰肽的开发：时间分辨小角中子散射研究

质膜中的磷脂跨双分子层的移动（触发器）由膜蛋白调节，以维持细胞稳态并与其他细胞相互作用。磷脂sc刺促进人字拖的增加导致膜脂质不对称性的丧失，这涉及细胞凋亡，血液凝固和病毒感染。因此，可以人工控制质膜中的触发器的化合物具有生物学和医学意义。在这里，我们开发了可插入膜的脂质加脂跨膜肽。时间分辨小角中子散射测量结果表明，在脂质序列的疏水序列中心包含谷氨酰胺残基的肽添加到脂质囊泡中会引起1-palmitoyl-2-oleoyl- sn的翻转-甘油-3-磷酸胆碱。没有谷氨酰胺残基的肽对触发器没有影响。因为含谷氨酰胺的肽以单体形式表现出乱糖酶活性，所以极性谷氨酰胺残基将暴露于膜的碳氢化合物区域，扰动膜并促进脂质翻转。这些加扰肽将是调节质膜中脂质翻转的有价值的工具。