Regulating the Membrane Transport Activity and Death of Cells via Electroosmotic Manipulation

Although the volume of living cells has been known to heavily influence their behavior and fate, a method allowing us to control the cell size in a programmable manner is still lacking. Here, we develop a technique in which precise changes in the cellular volume can be conveniently introduced by varying the voltage applied across a Nafion membrane that separates the culture medium from a reservoir. It is found that, unlike sudden osmotic shocks, active ion transport across the membrane of leukemia K562 cells will not be triggered by a gradual change in the extracellular osmolarity. Furthermore, when subjected to the same applied voltage, different lung and nasopharyngeal epithelial cancer cells will undergo larger volumetric changes and have a 5-10% higher death rate compared to their normal counterparts. We show that such distinct response is largely caused by the overexpression of aquaporin-4 in tumor cells, with knockout of this water channel protein resulting in a markedly reduced change in the cellular volume. Finally, by taking into account the exchange of water/ion molecules across the Nafion film and the cell membrane, a theoretical model is also proposed to describe the voltage-induced size changes of cells, which explain our experimental observations very well.