title: Regulating the Membrane Transport Activity and Death of Cells via Electroosmotic Manipulation.
abstract: 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.
authors.affiliation: Department of Mechanical Engineering, The University of Hong Kong, Hong Kong SAR, China; HKU-Shenzhen Institute of Research and Innovation (HKU-SIRI), Shenzhen, Guangdong, China.
authors.forename: Tsz Hin
authors.initials: TH
authors.lastname: Hui
authors.affiliation: Department of Mechanical Engineering, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kin Wah
authors.initials: KW
authors.lastname: Kwan
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China.
authors.forename: Timothy Tak
authors.initials: TT
authors.lastname: Chun Yip
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China.
authors.forename: Hong Wai
authors.initials: HW
authors.lastname: Fong
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China.
authors.forename: Kai Cheong
authors.initials: KC
authors.lastname: Ngan
authors.affiliation: Bioengineering Graduate Program, Biomedical Engineering Division, Hong Kong University of Science and Technology, Hong Kong SAR, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Bioengineering Graduate Program, Biomedical Engineering Division, Hong Kong University of Science and Technology, Hong Kong SAR, China; Department of Mechanical and Aerospace Engineering, Hong Kong University of Science and Technology, Hong Kong SAR, China.
authors.forename: Shuhuai
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Mechanical Engineering, The University of Hong Kong, Hong Kong SAR, China. Electronic address: hwngan@hku.hk.
authors.forename: Alfonso Hin
authors.initials: AH
authors.lastname: Wan Ngan
authors.affiliation: Department of Mechanical Engineering, The University of Hong Kong, Hong Kong SAR, China; HKU-Shenzhen Institute of Research and Innovation (HKU-SIRI), Shenzhen, Guangdong, China. Electronic address: ylin@hku.hk.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
mesh_terms: D051398:Aquaporin 1 / Q000378:metabolism; D051399:Aquaporin 2 / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D001693:Biological Transport, Active / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology; D048429:Cell Size; D004560:Electricity; D053841:Electroosmosis / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D005465:Fluorocarbon Polymers; D055786:Gene Knockout Techniques; D006801:Humans; D007477:Ions / Q000378:metabolism; D008567:Membranes, Artificial; D008954:Models, Biological; D014867:Water / Q000378:metabolism
chemical_list: C496020:AQP1 protein, human; C496023:AQP2 protein, human; C496030:AQP4 protein, human; D051399:Aquaporin 2; D051401:Aquaporin 4; D005465:Fluorocarbon Polymers; D007477:Ions; D008567:Membranes, Artificial; D014867:Water; D051398:Aquaporin 1; C040402:perfluorosulfonic acid