Monitoring impedance changes associated with motility and mitosis of a single cell.

We present a device enabling impedance measurements that probe the motility and mitosis of a single adherent cell in a controlled way. The micrometre-sized electrodes are designed for adhesion of an isolated cell and enhanced sensitivity to cell motion. The electrode surface is switched electro-chemically to favour cell adhesion, and single cells are attracted to the electrode using positive dielectrophoresis. Periods of linear variation in impedance with time correspond to the motility of a single cell adherent to the surface estimated at 0.6 μm h(-1). In the course of our study we observed the impedance changes associated with mitosis of a single cell. Electrical measurements, carried out concomitantly with optical observations, revealed three phases, prophase, metaphase and anaphase in the time variation of the impedance during cell division. Maximal impedance was observed at metaphase with a 20% increase of the impedance. We argue that at mitosis, the changes detected were due to the charge density distribution at the cell surface. Our data demonstrate subtle electrical changes associated with cell motility and for the first time with division at the single-cell level. We speculate that this could open up new avenues for characterizing healthy and pathological cells.

[1]  M. Fenech,et al.  Multiple origins of spontaneously arising micronuclei in HeLa cells: direct evidence from long-term live cell imaging. , 2008, Mutation research.

[2]  Deirdre R. Meldrum,et al.  Life-on-a-chip , 2003, Nature Reviews Microbiology.

[3]  Matsuhiko Nishizawa,et al.  Selective capture of a specific cell type from mixed leucocytes in an electrode-integrated microfluidic device. , 2009, Biosensors & bioelectronics.

[4]  P. Liberali,et al.  Population context determines cell-to-cell variability in endocytosis and virus infection , 2009, Nature.

[5]  M. Whitfield,et al.  Stem-Loop Binding Protein, the Protein That Binds the 3′ End of Histone mRNA, Is Cell Cycle Regulated by Both Translational and Posttranslational Mechanisms , 2000, Molecular and Cellular Biology.

[6]  T. Kirchhausen,et al.  Endosomal recycling controls plasma membrane area during mitosis , 2007, Proceedings of the National Academy of Sciences.

[7]  Matsuhiko Nishizawa,et al.  Patterning Adherent Cells within Microchannels by Combination of Electrochemical Biolithography Technique and Repulsive Dielectrophoretic Force , 2008 .

[8]  Ivar Giaever,et al.  Use of Electric Fields to Monitor the Dynamical Aspect of Cell Behavior in Tissue Culture , 1986, IEEE Transactions on Biomedical Engineering.

[9]  M. Nesladek,et al.  Transparent diamond‐on‐glass micro‐electrode arrays for ex‐vivo neuronal study , 2008 .

[10]  T. Brent,et al.  Changes in Surface Charge of HeLa Cells during the Cell Cycle , 1967, Nature.

[11]  I. Giaever,et al.  Patterns of oscillation during mitosis in plasmodia ofPhysarum polycephalum , 1995, Protoplasma.

[12]  A. Huttenlocher,et al.  Adhesion in cell migration. , 1995, Current opinion in cell biology.

[13]  P. Sorger,et al.  Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis , 2009, Nature.

[14]  Julian A. T. Dow,et al.  Single cell mobility and adhesion monitoring using extracellular electrodes , 1991 .

[15]  Kerry A Landman,et al.  Multi-scale modeling of a wound-healing cell migration assay. , 2007, Journal of theoretical biology.

[16]  Jing Zhu,et al.  An automatic and quantitative on-chip cell migration assay using self-assembled monolayers combined with real-time cellular impedance sensing. , 2008, Lab on a chip.

[17]  Jan Vijg,et al.  Increased cell-to-cell variation in gene expression in ageing mouse heart , 2006, Nature.

[18]  Natalie de Souza Single-cell methods , 2009, Nature Methods.

[19]  I. Giaever,et al.  Electric measurements can be used to monitor the attachment and spreading of cells in tissue culture. , 1991, BioTechniques.

[20]  I. Giaever,et al.  Combining optical and electrical impedance techniques for quantitative measurement of confluence in MDCK-I cell cultures. , 2004, BioTechniques.

[21]  Joachim Wegener,et al.  Electrical wound-healing assay for cells in vitro. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  T. Kirchhausen,et al.  Mammalian Cells Change Volume during Mitosis , 2008, PloS one.

[23]  Matsuhiko Nishizawa,et al.  Microelectrochemical approach to induce local cell adhesion and growth on substrates. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[24]  Cheng-Hsien Liu,et al.  Rapid heterogeneous liver-cell on-chip patterning via the enhanced field-induced dielectrophoresis trap. , 2006, Lab on a chip.

[25]  Youngmi Kim Pak,et al.  Fitting Improvement Using a New Electrical Circuit Model for the Electrode-Electrolyte Interface , 2007, 2007 3rd International IEEE/EMBS Conference on Neural Engineering.

[26]  J. Wegener,et al.  Electric cell-substrate impedance sensing (ECIS) as a noninvasive means to monitor the kinetics of cell spreading to artificial surfaces. , 2000, Experimental cell research.

[27]  S. Gawad,et al.  Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing. , 2001, Lab on a chip.

[28]  P. Friedl,et al.  Tumour-cell invasion and migration: diversity and escape mechanisms , 2003, Nature Reviews Cancer.