The distribution of surface charge and potential of cell membrane plays an indispensable role in cellular activities. However, probing surface charge of live cells under physiological conditions, until recently, remains an arduous challenge owing to the lack of effective methods. Scanning ion conductance microscopy (SICM) is an emerging imaging technique for imaging a live cell membrane in its native state. Here, we introduce a simple SICM based imaging technique to effectively map the surface charge contrast distribution of soft substrates including cell membranes by utilizing the higher surface charge sensitivity of the ionic current when the nanopipette tip is close to the substrate with a relatively high current change. This technique was assessed on charged model substrates made of polydimethylsiloxane, and the surface charge sensitivity of ionic current change was supported by finite element method simulations. With this method, we can distinguish the surface charge difference between the cell membrane and the supporting collagen matrix. We also observed the surface charge change induced by the small membrane damage after 1% dimethyl sulfoxide (DMSO) treatment. This new SICM technique provides opportunities to study interfacial and cell membrane processes with high spatial resolution.

中文翻译：

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使用扫描离子电导显微镜通过离子电流变化测量活细胞膜的表面电荷分布

细胞膜表面电荷和电位的分布在细胞活动中起着不可或缺的作用。然而，由于缺乏有效的方法，在生理条件下探测活细胞的表面电荷直到最近仍然是一项艰巨的挑战。扫描离子电导显微镜 (SICM) 是一种新兴的成像技术，用于对处于天然状态的活细胞膜进行成像。在这里，我们介绍了一种简单的基于 SICM 的成像技术，当纳米移液器尖端靠近具有相对较高电流变化的基板时，利用离子电流的更高表面电荷敏感性，有效地绘制包括细胞膜在内的软基板的表面电荷对比度分布. 该技术是在由聚二甲基硅氧烷制成的带电模型基板上进行评估的，离子电流变化的表面电荷敏感性得到了有限元方法模拟的支持。通过这种方法，我们可以区分细胞膜和支持胶原基质之间的表面电荷差异。我们还观察到在 1% 二甲基亚砜 (DMSO) 处理后由小的膜损伤引起的表面电荷变化。这种新的 SICM 技术为研究具有高空间分辨率的界面和细胞膜过程提供了机会。