Divalent Cation-Dependent Formation of Electrostatic PIP2 Clusters in Lipid Monolayers
Divalent Cation-Dependent Formation of Electrostatic PIP2 Clusters in Lipid Monolayers
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DOI：
10.1016/j.bpj.2011.09.039
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发表时间：
2011-11-02
影响因子：
3.4
通讯作者：
Liu, Andrea J.
中科院分区：
文献类型：
--
作者：
Ellenbroek, Wouter G.;Wang, Yu-Hsiu;Liu, Andrea J.
聚磷酸肌醇是细胞膜中电荷最高的分子之一，最常见的聚磷酸肌醇，磷脂酰肌醇-4，5-二磷酸（PIP 2），参与细胞膜中的许多机械和生物化学过程。二价阳离子如钙离子可引起聚阴离子PIP 2的聚集，但导致聚集的有效吸引力的来源和强度尚不清楚。此外，离子介导的吸引力是否足以改变膜的机械性质的问题，据我们所知，还没有得到解决。我们研究相分离的中性和高度负电荷的脂质混合单分子膜，诱导的二价正电荷的抗衡离子，实验和数值模拟。我们发现PIP 2和1-stearoyl-2-oleoyl磷脂酰胆碱的混合物的实验和模拟的简化模型，其中只有必要的静电相互作用被保留之间有很好的协议。此外，我们发现在一定条件下，有效吸引力可以刚性化所产生的集群。我们的研究结果支持的解释PIP 2集群主要由静电相互作用。在生理pH下，模拟表明，即使在PIP 2的总浓度很小的情况下，有效吸引力也足够强，可以产生几乎纯的PIP 2簇。
Polyphosphoinositides are among the most highly charged molecules in the cell membrane, and the most common polyphosphoinositide, phosphatidylinositol-4,5-bisphosphate (PIP2), is involved in many mechanical and biochemical processes in the cell membrane. Divalent cations such as calcium can cause clustering of the polyanionic PIP2, but the origin and strength of the effective attractions leading to clustering has been unclear. In addition, the question of whether the ion-mediated attractions could be strong enough to alter the mechanical properties of the membrane, to our knowledge, has not been addressed. We study phase separation in mixed monolayers of neutral and highly negatively charged lipids, induced by the addition of divalent positively charged counterions, both experimentally and numerically. We find good agreement between experiments on mixtures of PIP2 and 1-stearoyl-2-oleoyl phosphatidylcholine and simulations of a simplified model in which only the essential electrostatic interactions are retained. In addition, we find numerically that under certain conditions the effective attractions can rigidify the resulting clusters. Our results support an interpretation of PIP2 clustering as governed primarily by electrostatic interactions. At physiological pH, the simulations suggest that the effective attractions are strong enough to give nearly pure clusters of PIP2 even at small overall concentrations of PIP2.