Electromechanics and Volume Dynamics in Non-excitable Tissue Cells

Abstract

Cell volume regulation is fundamentally important in phenomena such as cell growth, proliferation, tissue homeostasis and embryogenesis. How the cell size is set, maintained, and changed over a cell's lifetime is not well understood. In this work we focus on how the volume of non-excitable tissue cells is coupled to the cell membrane electrical potential and the concentration of membrane-permeable ions in the cell environment. Specifically, we demonstrate that a sudden cell depolarization using the whole cell patch clamp results in a 30 percent increase in cell volume, while hyperpolarization results in a slight volume decrease. We find that cell volume can be partially controlled by changing the chloride or the sodium/potassium concentrations in the extracellular environment while maintaining a constant external osmotic pressure. Depletion of external chloride leads to a volume decrease in suspended HN31 cells.Introducing cells to a high potassium solution causes volume increase by up to 50%. Cell volume is also influenced by cortical tension: actin depolymerization leads to cell volume increase. We present an electrophysiology model of water dynamics driven by changes in membrane potential and in the concentration of permeable ions in the cell surrounding. The model quantitatively predicts that the cell volume is determined by the total amount of intracellular ion and protein content.

Interrogating the Electromechanical Regulation of Cellular Volume at the Single-Cell Level

“…In this issue of Biophysical Journal, Yellin et al (9) present a promising method that could address these outstanding problems. Specifically, by using the whole-cell patch-clamp setup, Yellin and co-workers were able to precisely control the membrane potential of a single cell as well as monitor its volume change in an accurate and continuous manner.…”

“…Interestingly, Yellin et al ( 9) also found that, even when the surrounding osmolarity was kept at the same level, altering the concentration percentage of chloride or potassium ions in the culture fluid led to distinct volumetric response of cells, highlighting the importance of cross-membrane transport of individual ion species in the volume regulation of cells. Fortunately, on the basis of the platform developed in (9), it becomes possible to quantitatively measure, after proper fluorescent labeling (8,10), how the concentrations of different intracellular ions evolve under precisely controlled experimental conditions (e.g., at fixed level of membrane potential and/or extracellular concentration of individual ions), which will greatly help us understand the mechanism(s) behind such transmembrane ion exchange. Finally, by taking into account both the passive and active (by different ion channels/pumps) cross-membrane transport of major ions as well as water molecules, Yellin et al (9) propose a mathematical model to quantitatively explain the observed volumetric response of cells under different electromechanical cues in their experiment.…”

“…Fortunately, on the basis of the platform developed in (9), it becomes possible to quantitatively measure, after proper fluorescent labeling (8,10), how the concentrations of different intracellular ions evolve under precisely controlled experimental conditions (e.g., at fixed level of membrane potential and/or extracellular concentration of individual ions), which will greatly help us understand the mechanism(s) behind such transmembrane ion exchange. Finally, by taking into account both the passive and active (by different ion channels/pumps) cross-membrane transport of major ions as well as water molecules, Yellin et al (9) propose a mathematical model to quantitatively explain the observed volumetric response of cells under different electromechanical cues in their experiment. Interestingly, the model also suggests that as cells grow and age, their volume will increase linearly with the total amount of cell proteins, whereas the concentrations of intracellular proteins and ions will remain more or less constant.…”