Bakhtiari Shide, Manshadi Mohammad K D, Candas Mehmet, Beskok Ali
Mechanical Engineering Department, Southern Methodist University, Dallas, TX 75275, USA.
Department of Biological Sciences, University of Texas at Dallas, Dallas, TX 75080, USA.
Micromachines (Basel). 2023 Jan 26;14(2):316. doi: 10.3390/mi14020316.
The plasma membrane is a lipid bilayer that establishes the outer boundary of a living cell. The composition of the lipid bilayer influences the membrane's biophysical properties, including fluidity, thickness, permeability, phase behavior, charge, elasticity, and formation of flat sheet or curved structures. Changes in the biophysical properties of the membrane can be occasioned when new entities, such as drug molecules, are partitioned in the bilayer. Therefore, assessing drugs for their effect on the biophysical properties of the lipid bilayer of a cell membrane is critical to understanding specific and non-specific drug action. Previously, we reported a non-invasive technique for real-time characterization of cellular dielectric properties, such as membrane capacitance and cytoplasmic conductivity. In this study, we discuss the potential application of the technique in assessing the biophysical properties of the cell membrane in response to interaction with amiodarone compared to aspirin/acetylsalicylic acid and glucose. Amiodarone is a potent drug used to treat cardiac arrhythmia, but it also exerts various non-specific effects. Compared to aspirin and glucose, we measured a rapid and higher magnitude increase in membrane capacitance on cells under amiodarone treatment. Increased membrane capacitance induced by aspirin and glucose quickly returned to baseline in 15 s, while amiodarone-induced increased capacitance sustained and decreased slowly, approaching baseline or another asymptotic limit in ~2.5 h. Because amiodarone has a strong lipid partitioning property, we reason that drug partitioning alters the lipid bilayer context and subsequently reduces bilayer thickness, leading to an increase in the electrical capacitance of the cell membrane. The presented microfluidic system promises a new approach to assess drug-membrane interactions and delineate specific and non-specific actions of the drug on cells.
质膜是一种脂质双层结构，它确立了活细胞的外部边界。脂质双层的组成会影响膜的生物物理性质，包括流动性、厚度、通透性、相行为、电荷、弹性以及平板或弯曲结构的形成。当新的实体（如药物分子）在双层中分配时，膜的生物物理性质可能会发生变化。因此，评估药物对细胞膜脂质双层生物物理性质的影响对于理解药物的特异性和非特异性作用至关重要。此前，我们报道了一种用于实时表征细胞介电性质（如膜电容和细胞质电导率）的非侵入性技术。在本研究中，我们讨论了该技术在评估细胞膜与胺碘酮、阿司匹林/乙酰水杨酸和葡萄糖相互作用时的生物物理性质方面的潜在应用。胺碘酮是一种用于治疗心律失常的强效药物，但它也会产生各种非特异性作用。与阿司匹林和葡萄糖相比，我们测量到在胺碘酮处理下细胞的膜电容迅速且有更大幅度的增加。阿司匹林和葡萄糖诱导的膜电容增加在15秒内迅速恢复到基线，而胺碘酮诱导的电容增加持续存在且下降缓慢，在约2.5小时内接近基线或另一个渐近极限。由于胺碘酮具有很强的脂质分配特性，我们推断药物分配改变了脂质双层环境，随后降低了双层厚度，导致细胞膜电容增加。所展示的微流控系统有望为评估药物 - 膜相互作用以及描绘药物对细胞的特异性和非特异性作用提供一种新方法。
