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微通道中通透细胞膜分子运输的理论研究

Theoretical Study of Molecular Transport Through a Permeabilized Cell Membrane in a Microchannel.

作者信息

Mahboubi Masoumeh, Movahed Saeid, Hosseini Abardeh Reza, Hoshyargar Vahid

机构信息

Department of Mechanical Engineering, Amirkabir University of Technology (Tehran Polytechnic), 424 Hafez Avenue, Tehran, 15875-4413, Iran.

Research Lab for Advanced Separation Processes, Department of Chemical Engineering, Iran University of Science and Technology, Narmak, Tehran, 16846-13114, Iran.

出版信息

J Membr Biol. 2017 Jun;250(3):285-299. doi: 10.1007/s00232-017-9961-2. Epub 2017 Apr 29.

DOI:10.1007/s00232-017-9961-2
PMID:28456838
Abstract

A two-dimensional model is developed to study the molecular transport into an immersed cell in a microchannel and to investigate the effects of finite boundary (a cell is suspended in a microchannel), amplitude of electric pulse, and geometrical parameter (microchannel height and size of electrodes) on cell uptake. Embedded electrodes on the walls of the microchannel generate the required electric pulse to permeabilize the cell membrane, pass the ions through the membrane, and transport them into the cell. The shape of electric pulses is square with the time span of 6 ms; their intensities are in the range of 2.2, 2.4, 2.6, 3 V. Numerical simulations have been performed to comprehensively investigate the molecular uptake into the cell. The obtained results of the current study demonstrate that calcium ions enter the cell from the anodic side (the side near positive electrode); after a while, the cell faces depletion of the calcium ions on a positive electrode-facing side within the microchannel; the duration of depletion depends on the amplitude of electric pulse and geometry that lasts from microseconds to milliseconds. By keeping geometrical parameters and time span constant, increment of a pulse intensity enhances molecular uptake and rate of propagation inside the cell. If a ratio of electrode size to cell diameter is larger than 1, the transported amount of Ca into the cell, as well as the rate of propagation, will be significantly increased. By increasing the height of the microchannel, the rate of uptake is decreased. In an infinite domain, the peak concentration becomes constant after reaching the maximum value; this value depends on the intra-extracellular conductivity and diffusion coefficient of interior and exterior domains of the cell. In comparison, the maximum concentration is changed by geometrical parameters in the microchannel. After reaching the maximum value, the peak concentration reduces due to the depletion of Ca ions within the microchannel. Electrophoretic velocity has a significant effect on the cell uptake.

摘要

开发了一个二维模型,以研究分子向微通道中浸没细胞的传输,并研究有限边界(细胞悬浮在微通道中)、电脉冲幅度和几何参数(微通道高度和电极尺寸)对细胞摄取的影响。微通道壁上的嵌入式电极产生所需的电脉冲,以使细胞膜通透,使离子穿过膜并将它们传输到细胞中。电脉冲的形状为方形,时间跨度为6毫秒;其强度范围为2.2、2.4、2.6、3伏。已进行数值模拟以全面研究分子向细胞中的摄取。当前研究获得的结果表明,钙离子从阳极侧(靠近正极的一侧)进入细胞;一段时间后,细胞在微通道内面向正极的一侧面临钙离子耗尽;耗尽的持续时间取决于电脉冲的幅度和几何形状,持续时间从微秒到毫秒不等。在保持几何参数和时间跨度不变的情况下,脉冲强度的增加会提高分子摄取和在细胞内的传播速率。如果电极尺寸与细胞直径的比率大于1,则进入细胞的Ca传输量以及传播速率将显著增加。通过增加微通道的高度,摄取速率会降低。在无限域中,峰值浓度在达到最大值后变得恒定;该值取决于细胞内外区域的细胞内-外电导率和扩散系数。相比之下,微通道中的几何参数会改变最大浓度。在达到最大值后,由于微通道内Ca离子的耗尽,峰值浓度会降低。电泳速度对细胞摄取有显著影响。

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微通道中单细胞双极(交流)脉冲电穿孔以在其膜上形成纳米孔的数值模拟。
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