Mapping surface charge density of lipid bilayers by quantitative surface conductivity microscopy.
Mapping surface charge density of lipid bilayers by quantitative surface conductivity microscopy.
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DOI：
10.1038/ncomms12447
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发表时间：
2016-08-26
影响因子：
16.6
通讯作者：
Dong, Mingdong
中科院分区：
文献类型：
--
作者：
Klausen, Lasse Hyldgaard;Fuhs, Thomas;Dong, Mingdong
脂质膜的局部表面电荷密度影响着所有活细胞中导致不同功能的膜-蛋白相互作用，它是理解膜结合机制、脂质体设计和药物传递的重要参数。尽管具有重要意义，但迄今为止还没有一种方法能够在生理相关条件下绘制表面电荷密度。在这里，我们使用扫描纳米吸管装置（扫描离子电导显微镜）结合一种新的算法来研究负载脂质双层附近的表面电导率，并提出了一种新的方法，定量表面电导率显微镜（QSCM），能够以高定量精度和纳米级分辨率绘制表面电荷密度。通过对纳米吸管尖端的离子电流进行广泛的理论分析，验证了该方法的有效性，并通过绘制模型阳离子、阴离子和两性离子脂质的表面电荷密度来证明QSCM的能力，结果与理论值精确匹配。脂质双层上的表面电荷深刻影响蛋白质与细胞膜相互作用的方式，但它们的精确量化已被证明具有挑战性。在这里，作者报告了一种在生理条件下绘制和评估表面电荷密度的定量方法。
Local surface charge density of lipid membranes influences membrane–protein interactions leading to distinct functions in all living cells, and it is a vital parameter in understanding membrane-binding mechanisms, liposome design and drug delivery. Despite the significance, no method has so far been capable of mapping surface charge densities under physiologically relevant conditions. Here, we use a scanning nanopipette setup (scanning ion-conductance microscope) combined with a novel algorithm to investigate the surface conductivity near supported lipid bilayers, and we present a new approach, quantitative surface conductivity microscopy (QSCM), capable of mapping surface charge density with high-quantitative precision and nanoscale resolution. The method is validated through an extensive theoretical analysis of the ionic current at the nanopipette tip, and we demonstrate the capacity of QSCM by mapping the surface charge density of model cationic, anionic and zwitterionic lipids with results accurately matching theoretical values. Surface charges on lipid bilayers deeply influence the way proteins interact with cellular membranes, yet their precise quantification has proven challenging. Here, the authors report on a quantitative method to map and evaluate surface charge densities under physiological conditions.
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