Effects of Concentration and Ionization Degree of Anchoring Cationic Polymers on the Lateral Heterogeneity of Anionic Lipid Monolayers.
Effects of Concentration and Ionization Degree of Anchoring Cationic Polymers on the Lateral Heterogeneity of Anionic Lipid Monolayers.
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DOI：
10.1021/acs.jpcb.6b12386
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发表时间：
2017-01
期刊：
影响因子：
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通讯作者：
Xiaozheng Duan;Yang Zhang;Liangyi Li;Ran Zhang;Mingming Ding;Qingrong Huang;Wen-Sheng Xu;T. Shi;L. An
中科院分区：
文献类型：
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作者：
Xiaozheng Duan;Yang Zhang;Liangyi Li;Ran Zhang;Mingming Ding;Qingrong Huang;Wen-Sheng Xu;T. Shi;L. An
我们采用粗粒度的Monte Carlo模拟研究了由阳离子聚合物和磷脂酰胆碱膜单层组成的系统，掺杂有单价阴离子磷脂酰丝氨酸（PS）和四价阴离子磷脂酰肌醇4，5-二磷酸（PIP2）脂质分子。对于这个系统，我们考虑的条件下，多个阳离子聚合物可以锚到单层上，并探讨如何聚合物的浓度和电离度影响的横向重排和流动性的带负电荷的脂质。我们的工作表明，锚定阳离子聚合物主要结合四价阴离子PIP2脂质，并拖动PIP2簇迁移到单层。发现聚合物/PIP2结合通过增加聚合物电离分数而显著增强，这导致PIP2脂质形成更大的簇并降低聚合物/PIP2复合物的流动性。正如预期的那样，锚定聚合物之间的竞争效应在较高的聚合物浓度下发生，其中每个锚定聚合物从单层部分解离，因此螯合较小的PIP2簇。锚定聚合物的脱附片段在膜上表现出更快的流动性，而PIP2簇被锚定聚合物的有限粘附阳离子片段紧密地限制。我们进一步证明了PIP2分子在PIP2簇中显示出分级流动性，这是由聚合物的阳离子片段之间的协同效应调节的。如果四价PIP2脂质不能充分中和阳离子聚合物，则PS脂质螯合在聚合物/PIP2复合物附近。最后，我们说明，在溶液中的离子浓度的增加削弱了横向集群和流动性的带电脂质的异质性。因此，我们的工作提供了一个更好的理解的基本生物物理机制的浓度梯度和层次流动性的阴离子脂质在膜上所造成的阳离子聚合物锚定的长度和时间尺度上，通常是不可访问的原子模型。它还提供了深入了解新的生物应用的基础上调制信号脂质的开发和设计。
We employed coarse-grained Monte Carlo simulations to investigate a system composed of cationic polymers and a phosphatidyl-choline membrane monolayer, doped with univalent anionic phosphatidylserine (PS) and tetravalent anionic phosphatidylinositol 4,5-bisphosphate (PIP2) lipid molecules. For this system, we consider the conditions under which multiple cationic polymers can anchor onto the monolayer and explore how the concentration and ionization degree of the polymers affect the lateral rearrangement and fluidity of the negatively charged lipids. Our work shows that the anchoring cationic polymers predominantly bind the tetravalent anionic PIP2 lipids and drag the PIP2 clusters to migrate on the monolayer. The polymer/PIP2 binding is found to be drastically enhanced by increasing the polymer ionization fraction, which causes the PIP2 lipids to form into larger clusters and reduces the mobility of the polymer/PIP2 complexes. As expected, stronger competition effects between anchoring polymers occur at higher polymer concentrations, for which each anchoring polymer partially dissociates from the monolayer and hence sequesters a smaller PIP2 cluster. The desorbed segments of the anchored polymers exhibit a faster mobility on the membrane, whereas the PIP2 clusters are closely restrained by the limited adhering cationic segments of anchoring polymers. We further demonstrate that the PIP2 molecules display a hierarchical mobility in the PIP2 clusters, which is regulated by the synergistic effect between the cationic segments of the polymers. The PS lipids sequester in the vicinity of the polymer/PIP2 complexes if the tetravalent PIP2 lipids cannot sufficiently neutralize the cationic polymers. Finally, we illustrate that the increase in the ionic concentration of the solution weakens the lateral clustering and the mobility heterogeneity of the charged lipids. Our work thus provides a better understanding of the fundamental biophysical mechanism of the concentration gradients and the hierarchical mobility of the anionic lipids in the membrane caused by the cationic polymer anchoring on length and time scales that are generally inaccessible by atomistic models. It also offers insight into the development and design of novel biological applications on the basis of the modulation of signaling lipids.