Li Yizeng, Zhou Xiaohan, Sun Sean X
Department of Mechanical Engineering, Kennesaw State University, Marietta, GA, United States.
Department of Physics, University of Toronto, Toronto, ON, Canada.
Front Cell Dev Biol. 2021 Jun 24;9:683686. doi: 10.3389/fcell.2021.683686. eCollection 2021.
Cells lacking a stiff cell wall, e.g., mammalian cells, must actively regulate their volume to maintain proper cell function. On the time scale that protein production is negligible, water flow in and out of the cell determines the cell volume variation. Water flux follows hydraulic and osmotic gradients; the latter is generated by various ion channels, transporters, and pumps in the cell membrane. Compared to the widely studied roles of sodium, potassium, and chloride in cell volume regulation, the effects of proton and bicarbonate are less understood. In this work, we use mathematical models to analyze how proton and bicarbonate, combined with sodium, potassium, chloride, and buffer species, regulate cell volume upon inhibition of ion channels, transporters, and pumps. The model includes several common, widely expressed ion transporters and focuses on obtaining generic outcomes. Results show that the intracellular osmolarity remains almost constant before and after cell volume change. The steady-state cell volume does not depend on water permeability. In addition, to ensure the stability of cell volume and ion concentrations, cells need to develop redundant mechanisms to maintain homeostasis, i.e., multiple ion channels or transporters are involved in the flux of the same ion species. These results provide insights for molecular mechanisms of cell volume regulation with additional implications for water-driven cell migration.
缺乏坚硬细胞壁的细胞，如哺乳动物细胞，必须积极调节其体积以维持正常的细胞功能。在蛋白质产生可忽略不计的时间尺度上，水进出细胞决定了细胞体积的变化。水通量遵循水力和渗透梯度；后者由细胞膜中的各种离子通道、转运体和泵产生。与钠、钾和氯在细胞体积调节中被广泛研究的作用相比，质子和碳酸氢根的作用了解较少。在这项工作中，我们使用数学模型来分析质子和碳酸氢根与钠、钾、氯和缓冲物质结合，在离子通道、转运体和泵受到抑制时如何调节细胞体积。该模型包括几种常见的、广泛表达的离子转运体，并专注于获得一般结果。结果表明，细胞体积变化前后细胞内渗透压几乎保持恒定。稳态细胞体积不依赖于水渗透性。此外，为确保细胞体积和离子浓度的稳定性，细胞需要发展冗余机制来维持内环境稳定，即多种离子通道或转运体参与同一离子种类的通量。这些结果为细胞体积调节的分子机制提供了见解，并对水驱动的细胞迁移有额外的启示。
