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Significant Elevation in Potassium Concentration Surrounding Stimulated Excitable Cells Revealed by an Aptamer-Modified Nanowire Transistor
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2021-08-27 , DOI: 10.1021/acsabm.1c00584
Ankur Anand, Hui-Chiun Tseng, Hsu-Cheng Chiang, Wan-Hsuan Hsu, Yi-Fan Liao, Serena Huei-An Lu, Su-Yi Tsai, Chien-Yuan Pan, Yit-Tsong Chen

Recording ion fluctuations surrounding biological cells with a nanoelectronic device offers seamless integration of nanotechnology into living organisms and is essential for understanding cellular activities. The concentration of potassium ion in the extracellular fluid () is a critical determinant of cell membrane potential and must be maintained within an appropriate range. Alteration in can affect neuronal excitability, induce heart arrhythmias, and even trigger seizure-like reactions in the brain. Therefore, monitoring local fluctuations in real time provides an early diagnosis of the occurrence of the K+-induced pathophysiological responses. Here, we modified the surface of a silicon nanowire field-effect transistor (SiNW-FET) with K+-specific DNA-aptamers (AptK+) to monitor the real-time variations of in primary cultured rat embryonic cortical neurons or human embryonic stem cell-derived cardiomyocytes. The binding affinity of AptK+ to K+, determined by measuring the dissociation constant of the AptK+–K+ complex (Kd = 10.1 ± 0.9 mM), is at least 38-fold higher than other ions (e.g., Na+, Ca2+, and Mg2+). By placing cultured cortical neurons over an AptK+/SiNW-FET device, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) stimulation raised the dose-dependently to 16 mM when AMPA concentration was >10 μM; this elevation could be significantly suppressed by an AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione. Likewise, the stimulation of isoproterenol to cardiomyocytes raised the to 6–8 mM, with a concomitant increase in the beating rate. This study utilizing a robust nanobiosensor to detect real-time ion fluctuations surrounding excitable cells underlies the importance of ion homeostasis and offers the feasibility of developing an implant device for real-time monitoring.

中文翻译:

适配体修饰的纳米线晶体管显示受激兴奋细胞周围钾浓度显着升高

使用纳米电子设备记录生物细胞周围的离子波动可以将纳米技术无缝集成到生物体中,这对于理解细胞活动至关重要。细胞外液中钾离子的浓度 ( ) 是细胞膜电位的关键决定因素,必须保持在适当的范围内。改变会影响神经元的兴奋性,诱发心律失常,甚至引发大脑中的癫痫样反应。因此,实时监测局部波动提供了对K +诱导的病理生理反应发生的早期诊断。在这里,我们用 K +修饰了硅纳米线场效应晶体管 (SiNW-FET) 的表面-特异性 DNA 适体 (Apt K + ),用于监测原代培养的大鼠胚胎皮质神经元或人胚胎干细胞衍生的心肌细胞的实时变化。通过测量 Apt K + –K +复合物的解离常数 ( K d = 10.1 ± 0.9 mM) 确定 Apt K +与 K +的结合亲和力比其他离子(例如 Na +、Ca 2+和Mg 2+ )。通过将培养的皮层神经元置于 Apt K +/SiNW-FET 器件,当 AMPA 浓度 >10 μM 时,α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 刺激剂量依赖性地提高到 16 mM;这种升高可以被 AMPA 受体拮抗剂 6,7-dinitroquinoxaline-2,3-dione 显着抑制。同样,异丙肾上腺素对心肌细胞的刺激提高到 6-8 mM,同时跳动率增加。本研究利用强大的纳米生物传感器来检测可兴奋细胞周围的实时离子波动,这是离子稳态的重要性的基础,并为开发用于实时监测的植入装置提供了可行性。
更新日期:2021-09-20
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