Inhibitory Effect of Lanthanides on Native Lipid Flip-Flop
Inhibitory Effect of Lanthanides on Native Lipid Flip-Flop
复制标题
镧系元素对天然脂质触发器的抑制作用
DOI：
10.1021/acs.jpcb.2c04039
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Conboy, John C.
中科院分区：
文献类型：
--
作者：
Cheng, Victoria;Conboy, John C.
研究了镱离子 (Yb3+)（一种常用的顺磁 NMR 化学位移试剂）对二棕榈酰磷脂酰胆碱 (DPPC) 平面支撑脂质双层 (PSLB) 的物理性质和翻转动力学的影响。 Langmuir 等温线研究表明，Yb3+ 与 DPPC 的磷酸盐头基发生强烈相互作用，剪切模量和压缩模量的增加证明了这一点。使用和频振动光谱，还观察到酰基链排序和相变温度的变化，这与 Yb3+ 与 DPPC 磷酸根头基的相互作用一致。还观察到膜物理性质的变化与浓度相关，与 6.5 mM Tb3+ 相比，在低 (50 μM) Yb3+ 浓度下观察到更明显的变化，表明相邻 DPPC 脂质之间存在交联机制。此外，在 Tris 缓冲液存在下膜填充和相变温度的变化表明假定的 Yb(Tris)3+ 复合物形式与 PC 头基协调。在 Yb3+ 存在下，无论 Yb3+ 浓度如何，凝胶相和液晶 (lc) 相中 DPPC 触发器的动力学都会受到显着抑制。在过渡态理论框架下对触发器动力学的分析表明，与纯 DPPC 膜相比，凝胶相和液晶相中触发器的自由能垒均显着增加。在凝胶相中，自由能垒的趋势似乎遵循剪切模量的趋势，表明Yb3+-DPPC头基相互作用正在驱动活化自由能垒的增加。在lc相中，发现50μM或6.5mM Yb3+存在下DPPC触发器的激活自由能反映了TEMPO-DPPC触发器的自由能，从而得出结论：Yb3+和PC头基之间的强相互作用本质上表现为头基电荷修饰。这些研究表明，镧系元素 Yb3+ 的存在会导致脂质膜物理性质的显着改变，更重要的是，会导致天然脂质触发器的显着抑制。
The influence of ytterbium ions (Yb3+), a commonly used paramagnetic NMR chemical shift reagent, on the physical properties and flip-flop kinetics of dipalmitoylphosphatidylcholine (DPPC) planar supported lipid bilayers (PSLBs) was investigated. Langmuir isotherm studies revealed that Yb3+interacts strongly with the phosphate headgroup of DPPC, evidenced by the increases in shear and compression moduli. Using sum-frequency vibrational spectroscopy, changes in the acyl chain ordering and phase transition temperature were also observed, consistent with Yb3+interacting with the phosphate headgroup of DPPC. The changes in the physical properties of the membrane were also observed to be concentration dependent, with more pronounced modification observed at low (50 μM) Yb3+concentrations compared to 6.5 mM Tb3+, suggesting a cross-linking mechanism between adjacent DPPC lipids. Additionally, the changes in membrane packing and phase transition temperatures in the presence of Tris buffer suggested that a putative Yb(Tris)3+complex forms that coordinates to the PC headgroup. The kinetics of DPPC flip-flop in the gel and liquid crystalline (lc) phases were substantially inhibited in the presence of Yb3+, regardless of the Yb3+concentration. Analysis of the flip-flop kinetics under the framework of transition state theory revealed that the free energy barrier to flip-flop in both the gel and lc phases was substantial increased over a pure DPPC membrane. In the gel phase, the trend in the free energy barrier appeared to follow the trend in the shear moduli, suggesting that the Yb3+–DPPC headgroup interaction was driving the increase in the activation free energy barrier. In the lc phase, activation free energies of DPPC flip-flop in the presence of 50 μM or 6.5 mM Yb3+were found to mirror the free energies of TEMPO–DPPC flip-flop, leading to the conclusion that the strong interaction between Yb3+and the PC headgroup was essentially manifested as a headgroup charge modification. These studies illustrate that the presence of the lanthanide Yb3+results in significant modification to the lipid membrane physical properties and, more importantly, results in a pronounced inhibition of native lipid flip-flop.