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首页> 外文期刊>Chemistry and Physics of Lipids >Comparative study on the interaction of cell-penetrating polycationic polymers with lipid membranes
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Comparative study on the interaction of cell-penetrating polycationic polymers with lipid membranes

机译：细胞穿透性聚阳离子聚合物与脂质膜相互作用的比较研究

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Cell-penetrating peptides are arginine- and lysine-rich cationic peptides that can readily enter cells not only by themselves but also carrying other macromolecular cargos. In fact, we have reported that polycationic polymer such as poly-l-lysine (PLL) and poly-l-arginine (PLA) translocate through negatively charged phospholipid liposome membranes. In this work, we made a comparative study of the interaction of PLL or PLA with lipid membranes consisting of negatively charged phospholipids to understand the role of basic amino acid residue (i.e. arginine and lysine) in the membrane-penetrating activity of polypeptides. PLA and PLL translocated into giant unilamellar vesicle composed of soybean phospholipids. ζ-potential and turbidity measurements demonstrated the electrostatic binding of PLL and PLA to large unilamellar vesicle (LUV). Fluorescence studies using membrane probes revealed that the binding of PLA and PLL to LUV affects the hydration and packing of the membrane interface region, in which the membrane insertion of PLA appeared to be greater than PLL. Differential scanning calorimetry showed that the enthalpy of the gel to liquid-crystalline phase transition for dipalmitoyl phosphatidylglycerol vesicle was greatly reduced by binding of PLL and PLA, in which the reduction is much larger in PLA than in PLL. Circular dichroism measurements in 2,2,2-trifluoroethanol/water mixture or in the presence of LUV indicated that the propensity of PLA to form α-helical structure is greater than PLL. Consistently, attenuated total reflection-Fourier transform infrared spectroscopy revealed that there is greater α-helical structure in PLA bound to LUV compared to PLL, which has much less ordered structure. Furthermore, isothermal titration calorimetry measurements demonstrated that the contribution of enthalpy to the energetics of binding to LUV is two-fold larger in PLA than in PLL. These results suggest that the stronger interaction of arginine residue with negatively charged phospholipid membranes compared to lysine residue appears to facilitate the conformational change in cationic polypeptide and its insertion into lipid membrane interior.
机译：细胞穿透肽是富含精氨酸和赖氨酸的阳离子肽，不仅可以自身进入细胞，还可以携带其他大分子货物进入细胞。实际上，我们已经报道了聚阳离子聚合物，例如聚-1-赖氨酸（PLL）和聚-1-精氨酸（PLA）通过带负电荷的磷脂脂质体膜移位。在这项工作中，我们对PLL或PLA与由带负电荷的磷脂组成的脂质膜的相互作用进行了比较研究，以了解碱性氨基酸残基（即精氨酸和赖氨酸）在多肽的膜穿透活性中的作用。 PLA和PLL易位到由大豆磷脂组成的巨大单层囊泡中。 ζ电位和浊度测量结果表明PLL和PLA与大单层囊泡（LUV）的静电结合。使用膜探针进行的荧光研究表明，PLA和PLL与LUV的结合会影响膜界面区域的水合作用和堆积，其中PLA的膜插入似乎大于PLL。差示扫描量热法显示，通过PLL和PLA的结合，二棕榈酰磷脂酰甘油囊泡的凝胶到液晶相变的焓大大降低，其中PLA的降低远大于PLL。在2,2,2-三氟乙醇/水混合物中或存在LUV的情况下进行圆二色性测量表明，PLA形成α螺旋结构的可能性大于PLL。一致地，衰减全反射-傅立叶变换红外光谱显示，与PLL相比，与LUV结合的PLA中具有更大的α螺旋结构，而PLL具有更少的有序结构。此外，等温滴定量热法测量表明，在PLA中，焓对结合LUV的能量的贡献比PLL大两倍。这些结果表明，与赖氨酸残基相比，精氨酸残基与带负电荷的磷脂膜的相互作用更强，似乎有助于阳离子多肽的构象变化及其插入脂质膜内部。

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