Skip to main content

Impedance-Based Assays Along the Life Span of Adherent Mammalian Cells In Vitro: From Initial Adhesion to Cell Death

  • Chapter
  • First Online:
Label-Free Monitoring of Cells in vitro

Part of the book series: Bioanalytical Reviews ((BIOREV,volume 2))

Abstract

Impedance-based monitoring of adherent cells has gained increasing acceptance in many areas of biomedical research and drug discovery, as it provides a noninvasive and label-free experimental tool to continuously monitor cell behavior in response to biological, chemical, or physical stimuli. It is based on growing cells on thin-film electrodes that are deposited on the bottom of regular cell cultureware and monitoring the electrical impedance of these electrodes as a function of frequency and time. Tailored hardware, data acquisition modes, electrode designs, and assay procedures have been developed for a fully automated and time-resolved observation of various cell phenotypes and phenotypic changes disclosed in cell-matrix adhesion, proliferation, differentiation, cell migration, signal transduction, or cell death. Impedance-based cell analysis is performed under regular cell culture conditions and applied for short-term and long-term observation of cell behaviour.

This review will recapitulate the physical principles of the measurement and highlight its applications not without critical assessment of its limitations. The most prominent impedance-based assays will be explained and discussed with reference to an extended literature survey of the field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AC:

Alternating current

BBB:

Blood-brain barrier

CBA:

Cell-based assays

DC:

Direct current

ECIS:

Electric cell-substrate impedance sensing

TEER:

Transendothelial/transepithelial epithelial electrical resistance

References

  1. Giaever I, Keese CR (1984) Monitoring fibroblast behavior in tissue culture with an applied electric field. Proc Natl Acad Sci U S A 81(12):3761–3764

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Giaever I, Keese CR (1991) Micromotion of mammalian cells measured electrically. Proc Natl Acad Sci U S A 88(17):7896–7900

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Keese CR, Giaever I (1991) Substrate mechanics and cell spreading. Exp Cell Res 195(2):528–532

    CAS  PubMed  Google Scholar 

  4. Lo CM, Keese CR, Giaever I (1993) Monitoring motion of confluent cells in tissue culture. Exp Cell Res 204(1):102–109

    CAS  PubMed  Google Scholar 

  5. Wegener J, Keese CR, Giaever I (2000) Electric cell-substrate impedance sensing (ECIS) as a noninvasive means to monitor the kinetics of cell spreading to artificial surfaces. Exp Cell Res 259(1):158–166

    CAS  PubMed  Google Scholar 

  6. Xiao C, Luong JH (2003) On-line monitoring of cell growth and cytotoxicity using electric cell-substrate impedance sensing (ECIS). Biotechnol Prog 19(3):1000–1005

    CAS  PubMed  Google Scholar 

  7. Wegener J, Seebach J (2014) Experimental tools to monitor the dynamics of endothelial barrier function: a survey of in vitro approaches. Cell Tissue Res 355(3):485–514

    CAS  PubMed  Google Scholar 

  8. Keese CR, Wegener J, Walker SR, Giaever I (2004) Electrical wound-healing assay for cells in vitro. Proc Natl Acad Sci U S A 101(6):1554–1559

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Tiruppathi C, Malik AB, Del Vecchio PJ, Keese CR, Giaever I (1992) Electrical method for detection of endothelial cell shape change in real time: assessment of endothelial barrier function. Proc Natl Acad Sci U S A 89(17):7919–7923

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Bagnaninchi PO, Drummond N (2011) Real-time label-free monitoring of adipose-derived stem cell differentiation with electric cell-substrate impedance sensing. Proc Natl Acad Sci U S A 108(16):6462–6467

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Stolwijk JA, Michaelis S, Wegener J (2012) Cell growth and cell death studied by electric cell-substrate impedance sensing. Electric cell-substrate impedance sensing and cancer metastasis. Springer, Heidelberg, pp 85–117

    Google Scholar 

  12. Dimitrov D (1995) Electroporation and electrofusion of membranes. Handb Biol Phys 1:851–901

    Google Scholar 

  13. Ramos C, Teissié J (2000) Electrofusion: a biophysical modification of cell membrane and a mechanism in exocytosis. Biochimie 82(5):511–518

    CAS  PubMed  Google Scholar 

  14. Barrau C, Teissie J, Gabriel B (2004) Osmotically induced membrane tension facilitates the triggering of living cell electropermeabilization. Bioelectrochemistry 63(1-2):327–332

    CAS  PubMed  Google Scholar 

  15. Tinoco I, Sauer K, Wang JC, Puglisi JD (1995) Physical chemistry: principles and applications in biological sciences, 4th edn. Prentice-Hall Inc., Upper Saddle River

    Google Scholar 

  16. Lojewska Z, Farkas DL, Ehrenberg B, Loew LM (1989) Analysis of the effect of medium and membrane conductance on the amplitude and kinetics of membrane potentials induced by externally applied electric fields. Biophys J 56(1):121–128

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Teissie J, Rols MP (1993) An experimental evaluation of the critical potential difference inducing cell membrane electropermeabilization. Biophys J 65(1):409–413

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Gross D, Loew LM, Webb WW (1986) Optical imaging of cell membrane potential changes induced by applied electric fields. Biophys J 50(2):339–348

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Riske KA, Dimova R (2005) Electro-deformation and portion of giant vesicles viewed with high temporal resolution. Biophys J 88(2):1143–1155

    CAS  PubMed  Google Scholar 

  20. Voldman J (2006) Electrical forces for microscale cell manipulation. Annu Rev Biomed Eng 8:425–454

    CAS  PubMed  Google Scholar 

  21. McCaig CD, Rajnicek AM, Song B, Zhao M (2005) Controlling cell behavior electrically: current views and future potential. Physiol Rev 85(3):943–978

    PubMed  Google Scholar 

  22. Zhao M, Forrester JV, McCaig CD (1999) A small, physiological electric field orients cell division. Proc Natl Acad Sci U S A 96(9):4942–4946

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Rajnicek AM, Foubister LE, McCaig CD (2006) Growth cone steering by a physiological electric field requires dynamic microtubules, microfilaments and Rac-mediated filopodial asymmetry. J Cell Sci 119(Pt 9):1736–1745

    CAS  PubMed  Google Scholar 

  24. Yao L, McCaig CD, Zhao M (2009) Electrical signals polarize neuronal organelles, direct neuron migration, and orient cell division. Hippocampus 19(9):855–868

    CAS  PubMed  Google Scholar 

  25. Yan X, Han J, Zhang Z, Wang J, Cheng Q, Gao K, Ni Y, Wang Y (2009) Lung cancer A549 cells migrate directionally in DC electric fields with polarized and activated EGFRs. Bioelectromagnetics 30(1):29–35

    PubMed  Google Scholar 

  26. Li J, Nandagopal S, Wu D, Romanuik SF, Paul K, Thomson DJ, Lin F (2011) Activated T lymphocytes migrate toward the cathode of DC electric fields in microfluidic devices. Lab Chip 11(7):1298–1304

    CAS  PubMed  Google Scholar 

  27. Gabriel B, Teissie J (1997) Direct observation in the millisecond time range of fluorescent molecule asymmetrical interaction with the electropermeabilized cell membrane. Biophys J 73(5):2630–2637

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Rols MP (2006) Electropermeabilization, a physical method for the delivery of therapeutic molecules into cells. Biochim Biophys Acta 1758(3):423–428

    CAS  PubMed  Google Scholar 

  29. Chen C, Smye SW, Robinson MP, Evans JA (2006) Membrane electroporation theories: a review. Med Biol Eng Comput 44(1-2):5–14

    CAS  PubMed  Google Scholar 

  30. Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH (1982) Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J 1(7):841–845

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Bernhardt J, Pauly H (1973) On the generation of potential differences across the membranes of ellipsoidal cells in an alternating electrical field. Biophysik 10(3):89–98

    CAS  PubMed  Google Scholar 

  32. Marszalek P, Liu DS, Tsong TY (1990) Schwan equation and transmembrane potential induced by alternating electric field. Biophys J 58(4):1053–1058

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Tsong TY (1991) Electroporation of cell membranes. Biophys J 60(2):297–306

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ghosh PM, Keese CR, Giaever I (1994) Morphological response of mammalian cells to pulsed ac fields. Bioelectrochem Bioenerg 33(2):121–133

    Google Scholar 

  35. Solly K, Wang X, Xu X, Strulovici B, Zheng W (2004) Application of real-time cell electronic sensing (RT-CES) technology to cell-based assays. Assay Drug Dev Technol 2(4):363–372

    CAS  PubMed  Google Scholar 

  36. Wegener J, Sieber M, Galla HJ (1996) Impedance analysis of epithelial and endothelial cell monolayers cultured on gold surfaces. J Biochem Biophys Methods 32(3):151–170

    CAS  PubMed  Google Scholar 

  37. Ghosh PM, Keese CR, Giaever I (1993) Monitoring electropermeabilization in the plasma membrane of adherent mammalian cells. Biophys J 64(5):1602–1609

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Xiao C, Lachance B, Sunahara G, Luong JH (2002) Assessment of cytotoxicity using electric cell-substrate impedance sensing: concentration and time response function approach. Anal Chem 74(22):5748–5753

    CAS  PubMed  Google Scholar 

  39. Duchateau S, Broeders J, Croux D, Janssen D, Rigo JM, Wagner P, Thoelen R, De Ceuninck W (2013) Cell proliferation monitoring by multiplexed electrochemical impedance spectroscopy on microwell assays. Phys Status Solidi C 10(5):882–888

    CAS  Google Scholar 

  40. Ende D, Mangold K (1993) Impedance spectroscopy. Chem Unserer Zeit 27(3):134–140

    CAS  Google Scholar 

  41. Chang B-Y, Park S-M (2010) Electrochemical impedance spectroscopy. Annu Rev Anal Chem 3:207–229

    CAS  Google Scholar 

  42. Lukic S, Wegener J (2015) Impedimetric monitoring of cell-based assays. Encyclopedia of life sciences. Wiley, Chichester

    Google Scholar 

  43. Khalil SF, Mohktar MS, Ibrahim F (2014) The theory and fundamentals of bioimpedance analysis in clinical status monitoring and diagnosis of diseases. Sensors 14(6):10895–10928

    PubMed  PubMed Central  Google Scholar 

  44. Daniels BP, Cruz-Orengo L, Pasieka TJ, Couraud PO, Romero IA, Weksler B, Cooper JA, Doering TL, Klein RS (2013) Immortalized human cerebral microvascular endothelial cells maintain the properties of primary cells in an in vitro model of immune migration across the blood brain barrier. J Neurosci Methods 212(1):173–179

    CAS  PubMed  Google Scholar 

  45. Nakagawa S, Deli MA, Kawaguchi H, Shimizudani T, Shimono T, Kittel A, Tanaka K, Niwa M (2009) A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochem Int 54(3–4):253–263

    CAS  PubMed  Google Scholar 

  46. Paolinelli R, Corada M, Ferrarini L, Devraj K, Artus C, Czupalla CJ, Rudini N, Maddaluno L, Papa E, Engelhardt B, Couraud PO, Liebner S, Dejana E (2013) Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro. PLoS One 8(8):e70233

    CAS  PubMed  PubMed Central  Google Scholar 

  47. von Wedel-Parlow M, Schrot S, Lemmen J, Treeratanapiboon L, Wegener J, Galla HJ (2011) Neutrophils cross the BBB primarily on transcellular pathways: an in vitro study. Brain Res 1367:62–76

    Google Scholar 

  48. Karczewski J, Troost FJ, Konings I, Dekker J, Kleerebezem M, Brummer RJ, Wells JM (2010) Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Gastrointest Liver Physiol 298(6):G851–G859

    CAS  PubMed  Google Scholar 

  49. Rehder D, Iden S, Nasdala I, Wegener J, Brickwedde MK, Vestweber D, Ebnet K (2006) Junctional adhesion molecule-a participates in the formation of apico-basal polarity through different domains. Exp Cell Res 312(17):3389–3403

    CAS  PubMed  Google Scholar 

  50. Wegener J, Abrams D, Willenbrink W, Galla HJ, Janshoff A (2004) Automated multi-well device to measure transepithelial electrical resistances under physiological conditions. Biotechniques 37(4):590, 592–594, 596–597

    CAS  PubMed  Google Scholar 

  51. Hu G-W, Li Q, Niu X, Hu B, Liu J, Zhou S-M, Guo S-C, Lang H-l, Zhang C-Q, Wang Y (2015) Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice. Stem Cell Res Ther 6(1):1

    Google Scholar 

  52. Martinez-Serra J, Gutierrez A, Muñoz-Capó S, Navarro-Palou M, Ros T, Amat JC, Lopez B, Marcus TF, Fueyo L, Suquia AG (2014) xCELLigence system for real-time label-free monitoring of growth and viability of cell lines from hematological malignancies. Onco Targets Ther 7:985

    PubMed  PubMed Central  Google Scholar 

  53. Volakis LI, Li R, Ackerman WE, Mihai C, Bechel M, Summerfield TL, Ahn CS, Powell HM, Zielinski R, Rosol TJ, Ghadiali SN, Kniss DA (2014) Loss of myoferlin redirects breast cancer cell motility towards collective migration. PLoS One 9(2):e86110

    PubMed  PubMed Central  Google Scholar 

  54. Stolwijk JA, Matrougui K, Renken CW, Trebak M (2015) Impedance analysis of GPCR-mediated changes in endothelial barrier function: overview and fundamental considerations for stable and reproducible measurements. Pflugers Arch 467(10):2193–2218

    CAS  PubMed  Google Scholar 

  55. Bokel C, Brown NH (2002) Integrins in development: moving on, responding to, and sticking to the extracellular matrix. Dev Cell 3(3):311–321

    CAS  PubMed  Google Scholar 

  56. Harburger DS, Calderwood DA (2009) Integrin signalling at a glance. J Cell Sci 122(Pt 2):159–163

    CAS  PubMed  Google Scholar 

  57. Michaelis S, Robelek R, Wegener J (2011) Studying cell–surface interactions in vitro: a survey of experimental approaches and techniques. Tissue engineering III: cell-surface interactions for tissue culture. Springer, Berlin, pp 33–66

    Google Scholar 

  58. Giacomello E, Neumayer J, Colombatti A, Perris R (1999) Centrifugal assay for fluorescence-based cell adhesion adapted to the analysis of ex vivo cells and capable of determining relative binding strengths. Biotechniques 26(4):758–762, 764–756

    CAS  PubMed  Google Scholar 

  59. Reyes CD, Garcia AJ (2003) A centrifugation cell adhesion assay for high-throughput screening of biomaterial surfaces. J Biomed Mater Res A 67(1):328–333

    PubMed  Google Scholar 

  60. Khalili AA, Ahmad MR (2015) A review of cell adhesion studies for biomedical and biological applications. Int J Mol Sci 16(8):18149–18184

    CAS  PubMed  Google Scholar 

  61. Wegener J, Keese CR, Giaever I (2002) Recovery of adherent cells after in situ electroporation monitored electrically. Biotechniques 33(2):348, 350, 352

    CAS  PubMed  Google Scholar 

  62. Mitra P, Keese CR, Giaever I (1991) Electric measurements can be used to monitor the attachment and spreading of cells in tissue culture. Biotechniques 11(4):504–510

    CAS  PubMed  Google Scholar 

  63. Frisch T, Thoumine O (2002) Predicting the kinetics of cell spreading. J Biomech 35(8):1137–1141

    PubMed  Google Scholar 

  64. Dubin-Thaler BJ, Giannone G, Dobereiner HG, Sheetz MP (2004) Nanometer analysis of cell spreading on matrix-coated surfaces reveals two distinct cell states and STEPs. Biophys J 86(3):1794–1806

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Cuvelier D, Thery M, Chu YS, Dufour S, Thiery JP, Bornens M, Nassoy P, Mahadevan L (2007) The universal dynamics of cell spreading. Curr Biol 17(8):694–699

    CAS  PubMed  Google Scholar 

  66. Sapper A, Reiss B, Janshoff A, Wegener J (2006) Adsorption and fluctuations of giant liposomes studied by electrochemical impedance measurements. Langmuir 22(2):676–680

    CAS  PubMed  Google Scholar 

  67. Castaneda FE, Walia B, Vijay-Kumar M, Patel NR, Roser S, Kolachala VL, Rojas M, Wang L, Oprea G, Garg P, Gewirtz AT, Roman J, Merlin D, Sitaraman SV (2005) Targeted deletion of metalloproteinase 9 attenuates experimental colitis in mice: central role of epithelial-derived MMP. Gastroenterology 129(6):1991–2008

    CAS  PubMed  Google Scholar 

  68. Driss A, Charrier L, Yan Y, Nduati V, Sitaraman S, Merlin D (2006) Dystroglycan receptor is involved in integrin activation in intestinal epithelia. Am J Physiol Gastrointest Liver Physiol 290(6):G1228–G1242

    CAS  PubMed  Google Scholar 

  69. Nguyen HT, Dalmasso G, Yan Y, Laroui H, Dahan S, Mayer L, Sitaraman SV, Merlin D (2010) MicroRNA-7 modulates CD98 expression during intestinal epithelial cell differentiation. J Biol Chem 285(2):1479–1489

    CAS  PubMed  Google Scholar 

  70. Navdaev A, Heitmann V, Desantana Evangelista K, Morgelin M, Wegener J, Eble JA (2008) The C-terminus of the gamma 2 chain but not of the beta 3 chain of laminin-332 is indirectly but indispensably necessary for integrin-mediated cell reactions. Exp Cell Res 314(3):489–497

    CAS  PubMed  Google Scholar 

  71. Luong JH, Habibi-Rezaei M, Meghrous J, Xiao C, Male KB, Kamen A (2001) Monitoring motility, spreading, and mortality of adherent insect cells using an impedance sensor. Anal Chem 73(8):1844–1848

    CAS  PubMed  Google Scholar 

  72. Luong JH, Xiao C, Lachance B, Leabu ŠM, Li X, Uniyal S, Chan BM (2004) Extended applications of electric cell-substrate impedance sensing for assessment of the structure–function of α2β1 integrin. Anal Chim Acta 501(1):61–69

    CAS  Google Scholar 

  73. Heijink IH, Brandenburg SM, Noordhoek JA, Postma DS, Slebos DJ, van Oosterhout AJ (2010) Characterisation of cell adhesion in airway epithelial cell types using electric cell-substrate impedance sensing. Eur Respir J 35(4):894–903

    CAS  PubMed  Google Scholar 

  74. Ehret R, Baumann W, Brischwein M, Schwinde A, Wolf B (1998) On-line control of cellular adhesion with impedance measurements using interdigitated electrode structures. Med Biol Eng Comput 36(3):365–370

    CAS  PubMed  Google Scholar 

  75. Atienza JM, Zhu J, Wang X, Xu X, Abassi Y (2005) Dynamic monitoring of cell adhesion and spreading on microelectronic sensor arrays. J Biomol Screen 10(8):795–805

    CAS  PubMed  Google Scholar 

  76. Sharma KV, Koenigsberger C, Brimijoin S, Bigbee JW (2001) Direct evidence for an adhesive function in the noncholinergic role of acetylcholinesterase in neurite outgrowth. J Neurosci Res 63(2):165–175

    CAS  PubMed  Google Scholar 

  77. van Gils JM, Stutterheim J, van Duijn TJ, Zwaginga JJ, Porcelijn L, de Haas M, Hordijk PL (2009) HPA-1a alloantibodies reduce endothelial cell spreading and monolayer integrity. Mol Immunol 46(3):406–415

    PubMed  Google Scholar 

  78. Asphahani F, Thein M, Veiseh O, Edmondson D, Kosai R, Veiseh M, Xu J, Zhang M (2008) Influence of cell adhesion and spreading on impedance characteristics of cell-based sensors. Biosens Bioelectron 23(8):1307–1313

    CAS  PubMed  Google Scholar 

  79. ten Klooster JP, Jaffer ZM, Chernoff J, Hordijk PL (2006) Targeting and activation of Rac1 are mediated by the exchange factor beta-Pix. J Cell Biol 172(5):759–769

    PubMed  PubMed Central  Google Scholar 

  80. Charboneau AL, Singh V, Yu T, Newsham IF (2002) Suppression of growth and increased cellular attachment after expression of DAL-1 in MCF-7 breast cancer cells. Int J Cancer 100(2):181–188

    CAS  PubMed  Google Scholar 

  81. Davies S, Jiang WG (2010) ALCAM, activated leukocyte cell adhesion molecule, influences the aggressive nature of breast cancer cells, a potential connection to bone metastasis. Anticancer Res 30(4):1163–1168

    CAS  PubMed  Google Scholar 

  82. Jiang WG, Ye L, Sanders AJ, Ruge F, Kynaston HG, Ablin RJ, Mason MD (2013) Prostate transglutaminase (TGase-4, TGaseP) enhances the adhesion of prostate cancer cells to extracellular matrix, the potential role of TGase-core domain. J Transl Med 11:269

    PubMed  PubMed Central  Google Scholar 

  83. Abassi YA, Xi B, Zhang W, Ye P, Kirstein SL, Gaylord MR, Feinstein SC, Wang X, Xu X (2009) Kinetic cell-based morphological screening: prediction of mechanism of compound action and off-target effects. Chem Biol 16(7):712–723

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Sawhney RS, Zhou GH, Humphrey LE, Ghosh P, Kreisberg JI, Brattain MG (2002) Differences in sensitivity of biological functions mediated by epidermal growth factor receptor activation with respect to endogenous and exogenous ligands. J Biol Chem 277(1):75–86

    CAS  PubMed  Google Scholar 

  85. Okochi M, Nomura S, Kaga C, Honda H (2008) Peptide array-based screening of human mesenchymal stem cell-adhesive peptides derived from fibronectin type III domain. Biochem Biophys Res Commun 371(1):85–89

    CAS  PubMed  Google Scholar 

  86. Yun Y, Dong Z, Tan Z, Schulz MJ (2010) Development of an electrode cell impedance method to measure osteoblast cell activity in magnesium-conditioned media. Anal Bioanal Chem 396(8):3009–3015. https://doi.org/10.1007/s00216-010-3521-2

    Article  CAS  PubMed  Google Scholar 

  87. Kundranda MN, Ray S, Saria M, Friedman D, Matrisian LM, Lukyanov P, Ochieng J (2004) Annexins expressed on the cell surface serve as receptors for adhesion to immobilized fetuin-A. Biochim Biophys Acta 1693(2):111–123

    CAS  PubMed  Google Scholar 

  88. Aikio M, Alahuhta I, Nurmenniemi S, Suojanen J, Palovuori R, Teppo S, Sorsa T, Lopez-Otin C, Pihlajaniemi T, Salo T, Heljasvaara R, Nyberg P (2012) Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma. PLoS One 7(12):e51044

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Ablin RJ, Kynaston HG, Mason MD, Jiang WG (2011) Prostate transglutaminase (TGase-4) antagonizes the anti-tumour action of MDA-7/IL-24 in prostate cancer. J Transl Med 9:49

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Du P, Ye L, Ruge F, Yang Y, Jiang WG (2011) Metastasis suppressor-1, MTSS1, acts as a putative tumour suppressor in human bladder cancer. Anticancer Res 31(10):3205–3212

    CAS  PubMed  Google Scholar 

  91. Lee CC, Putnam AJ, Miranti CK, Gustafson M, Wang LM, Vande Woude GF, Gao CF (2004) Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis. Oncogene 23(30):5193–5202

    CAS  PubMed  Google Scholar 

  92. Negash S, Wang HS, Gao C, Ledee D, Zelenka P (2002) Cdk5 regulates cell-matrix and cell-cell adhesion in lens epithelial cells. J Cell Sci 115(Pt 10):2109–2117

    CAS  PubMed  Google Scholar 

  93. Nethe M, Anthony EC, Fernandez-Borja M, Dee R, Geerts D, Hensbergen PJ, Deelder AM, Schmidt G, Hordijk PL (2010) Focal-adhesion targeting links caveolin-1 to a Rac1-degradation pathway. J Cell Sci 123(Pt 11):1948–1958

    CAS  PubMed  Google Scholar 

  94. Rotundo RF, Curtis TM, Shah MD, Gao B, Mastrangelo A, LaFlamme SE, Saba TM (2002) TNF-alpha disruption of lung endothelial integrity: reduced integrin mediated adhesion to fibronectin. Am J Physiol Lung Cell Mol Physiol 282(2):L316–L329

    CAS  PubMed  Google Scholar 

  95. Schmidt MH, Chen B, Randazzo LM, Bogler O (2003) SETA/CIN85/Ruk and its binding partner AIP1 associate with diverse cytoskeletal elements, including FAKs, and modulate cell adhesion. J Cell Sci 116(Pt 14):2845–2855

    CAS  PubMed  Google Scholar 

  96. Witzel F, Fritsche-Guenther R, Lehmann N, Sieber A, Bluthgen N (2015) Analysis of impedance-based cellular growth assays. Bioinformatics 31(16):2705–2712

    CAS  PubMed  Google Scholar 

  97. Pick H, Terrettaz S, Baud O, Laribi O, Brisken C, Vogel H (2013) Monitoring proliferative activities of hormone-like odorants in human breast cancer cells by gene transcription profiling and electrical impedance spectroscopy. Biosens Bioelectron 50:431–436

    CAS  PubMed  Google Scholar 

  98. Chakraborty PK, Lee WK, Molitor M, Wolff NA, Thevenod F (2010) Cadmium induces Wnt signaling to upregulate proliferation and survival genes in sub-confluent kidney proximal tubule cells. Mol Cancer 9:102

    PubMed  PubMed Central  Google Scholar 

  99. Horimoto N, Kitamura S, Tsuji K, Makino H (2014) Mizoribine inhibits the proliferation of renal stem/progenitor cells by G1/S arrest during renal regeneration. Acta Med Okayama 68(1):7–15

    CAS  PubMed  Google Scholar 

  100. Wang L, Wang L, Yin H, Xing W, Yu Z, Guo M, Cheng J (2010) Real-time, label-free monitoring of the cell cycle with a cellular impedance sensing chip. Biosens Bioelectron 25(5):990–995

    CAS  PubMed  Google Scholar 

  101. Masanetz S, Kaufmann C, Letzel T, Pfaff M (2012) Effects of pine pollen extracts on the proliferation and mRNA expression of porcine ileal cell cultures. J Appl Bot Food Qual 83(1):14–18

    Google Scholar 

  102. Broeders J, Duchateau S, Van Grinsven B, Vanaken W, Peeters M, Cleij T, Thoelen R, Wagner P, De Ceuninck W (2011) Miniaturised eight-channel impedance spectroscopy unit as sensor platform for biosensor applications. Phys Status Solidi A 208(6):1357–1363

    CAS  Google Scholar 

  103. Limame R, Wouters A, Pauwels B, Fransen E, Peeters M, Lardon F, De Wever O, Pauwels P (2012) Comparative analysis of dynamic cell viability, migration and invasion assessments by novel real-time technology and classic endpoint assays. PLoS One 7(10):e46536

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Chen SW, Yang JM, Yang JH, Yang SJ, Wang JS (2012) A computational modeling and analysis in cell biological dynamics using electric cell-substrate impedance sensing (ECIS). Biosens Bioelectron 33(1):196–203

    CAS  PubMed  Google Scholar 

  105. Voltan R, Zauli G, Rizzo P, Fucili A, Pannella M, Marci R, Tisato V, Ferrari R, Secchiero P (2014) In vitro endothelial cell proliferation assay reveals distinct levels of proangiogenic cytokines characterizing sera of healthy subjects and of patients with heart failure. Mediators Inflamm 2014:257081

    PubMed  PubMed Central  Google Scholar 

  106. Dowling CM, Ors CH, Kiely PA (2014) Using real-time impedance-based assays to monitor the effects of fibroblast-derived media on the adhesion, proliferation, migration and invasion of colon cancer cells. Biosci Rep 34(4):e00126

    PubMed  PubMed Central  Google Scholar 

  107. Horimoto N, Kitamura S, Tsuji K, Makino H (2013) Mizoribine inhibits the proliferation of renal stem/progenitor cells by G1/S arrest during renal regeneration. Acta Med Okayama 68(1):7–15

    Google Scholar 

  108. Kim JH, Jekarl DW, Kim M, Oh EJ, Kim Y, Park IY, Shin JC (2014) Effects of ECM protein mimetics on adhesion and proliferation of chorion derived mesenchymal stem cells. Int J Med Sci 11(3):298–308

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Cai C, Rodepeter FR, Rossmann A, Teymoortash A, Lee JS, Quint K, Pietro DIF, Ocker M, Werner JA, Mandic R (2012) SIVmac(2)(3)(9)-Nef down-regulates cell surface expression of CXCR4 in tumor cells and inhibits proliferation, migration and angiogenesis. Anticancer Res 32(7):2759–2768

    CAS  PubMed  Google Scholar 

  110. Danussi C, Petrucco A, Wassermann B, Pivetta E, Modica TM, Del Bel BL, Colombatti A, Spessotto P (2011) EMILIN1-alpha4/alpha9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. J Cell Biol 195(1):131–145

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Yuan SY, Rigor RR (2010) Regulation of endothelial barrier function. Integrated systems physiology: from molecule to function to disease. Morgan & Claypool Life Sciences, San Rafael

    Google Scholar 

  112. Wang Y, Alexander JS (2011) Analysis of endothelial barrier function in vitro. Methods Mol Biol 763:253–264

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Monaghan-Benson E, Wittchen ES (2011) In vitro analyses of endothelial cell permeability. Methods Mol Biol 763:281–290

    CAS  PubMed  Google Scholar 

  114. Benson K, Cramer S, Galla HJ (2013) Impedance-based cell monitoring: barrier properties and beyond. Fluids Barriers CNS 10(1):5

    PubMed  PubMed Central  Google Scholar 

  115. Hajek K, Wegener J (2017) Independent impedimetric analysis of two cell populations co-cultured on opposite sides of a porous support. Exp Cell Res 351(1):121–126

    CAS  PubMed  Google Scholar 

  116. Cecchelli R, Aday S, Sevin E, Almeida C, Culot M, Dehouck L, Coisne C, Engelhardt B, Dehouck MP, Ferreira L (2014) A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells. PLoS One 9(6):e99733

    PubMed  PubMed Central  Google Scholar 

  117. Dewi BE, Takasaki T, Kurane I (2004) In vitro assessment of human endothelial cell permeability: effects of inflammatory cytokines and dengue virus infection. J Virol Methods 121(2):171–180

    CAS  PubMed  Google Scholar 

  118. Schnoor M, Lai FP, Zarbock A, Klaver R, Polaschegg C, Schulte D, Weich HA, Oelkers JM, Rottner K, Vestweber D (2011) Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo. J Exp Med 208(8):1721–1735

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Hoheisel D, Nitz T, Franke H, Wegener J, Hakvoort A, Tilling T, Galla HJ (1998) Hydrocortisone reinforces the blood-brain barrier properties in a serum free cell culture system. Biochem Biophys Res Commun 244(1):312–316

    CAS  PubMed  Google Scholar 

  120. von Wedel-Parlow M, Wolte P, Galla HJ (2009) Regulation of major efflux transporters under inflammatory conditions at the blood-brain barrier in vitro. J Neurochem 111(1):111–118

    Google Scholar 

  121. Malina KC-K, Cooper I, Teichberg VI (2009) Closing the gap between the in-vivo and in-vitro blood–brain barrier tightness. Brain Res 1284:12–21

    Google Scholar 

  122. Schneider D, Tarantola M, Janshoff A (2011) Dynamics of TGF-beta induced epithelial-to-mesenchymal transition monitored by electric cell-substrate impedance sensing. Biochim Biophys Acta 1813(12):2099–2107

    CAS  PubMed  Google Scholar 

  123. Spiering D, Schmolke M, Ohnesorge N, Schmidt M, Goebeler M, Wegener J, Wixler V, Ludwig S (2009) MEK5/ERK5 signaling modulates endothelial cell migration and focal contact turnover. J Biol Chem 284(37):24972–24980

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Ko KS-C, Lo C-M, Ferrier J, Hannam P, Tamura M, McBride BC, Ellen RP (1998) Cell–substrate impedance analysis of epithelial cell shape and micromotion upon challenge with bacterial proteins that perturb extracellular matrix and cytoskeleton. J Microbiol Methods 34(2):125–132

    CAS  Google Scholar 

  125. Lovelady DC, Richmond TC, Maggi AN, Lo CM, Rabson DA (2007) Distinguishing cancerous from noncancerous cells through analysis of electrical noise. Phys Rev E Stat Nonlinear Soft Matter Phys 76(4 Pt 1):041908

    CAS  Google Scholar 

  126. Tarantola M, Marel AK, Sunnick E, Adam H, Wegener J, Janshoff A (2010) Dynamics of human cancer cell lines monitored by electrical and acoustic fluctuation analysis. Integr Biol 2(2–3):139–150

    CAS  Google Scholar 

  127. Sawhney RS, Sharma B, Humphrey LE, Brattain MG (2003) Integrin α2 and extracellular signal-regulated kinase are functionally linked in highly malignant autocrine transforming growth factor-α-driven colon cancer cells. J Biol Chem 278(22):19861–19869

    CAS  PubMed  Google Scholar 

  128. Giaever I, Keese C (1989) Fractal motion of mammalian cells. Physica D 38(1–3):128–133

    Google Scholar 

  129. Lovelady DC, Friedman J, Patel S, Rabson DA, Lo CM (2009) Detecting effects of low levels of cytochalasin B in 3T3 fibroblast cultures by analysis of electrical noise obtained from cellular micromotion. Biosens Bioelectron 24(7):2250–2254

    CAS  PubMed  Google Scholar 

  130. Opp D, Wafula B, Lim J, Huang E, Lo J-C, Lo C-M (2009) Use of electric cell–substrate impedance sensing to assess in vitro cytotoxicity. Biosens Bioelectron 24(8):2625–2629

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Tarantola M, Schneider D, Sunnick E, Adam H, Pierrat S, Rosman C, Breus V, Sonnichsen C, Basché T, Wegener J (2008) Cytotoxicity of metal and semiconductor nanoparticles indicated by cellular micromotility. ACS Nano 3(1):213–222

    Google Scholar 

  132. Tarantola M, Sunnick E, Schneider D, Marel AK, Kunze A, Janshoff A (2011) Dynamic changes of acoustic load and complex impedance as reporters for the cytotoxicity of small molecule inhibitors. Chem Res Toxicol 24(9):1494–1506

    CAS  PubMed  Google Scholar 

  133. Lang O, Kohidai L, Wegener J (2017) Label-free profiling of cell dynamics: a sequence of impedance-based assays to estimate tumor cell invasiveness in vitro. Exp Cell Res 359(1):243–250

    CAS  PubMed  Google Scholar 

  134. Lo CM, Keese CR, Giaever I (1994) pH changes in pulsed CO2 incubators cause periodic changes in cell morphology. Exp Cell Res 213(2):391–397

    CAS  PubMed  Google Scholar 

  135. Das D, Shiladitya K, Biswas K, Dutta PK, Parekh A, Mandal M, Das S (2015) Wavelet-based multiscale analysis of bioimpedance data measured by electric cell-substrate impedance sensing for classification of cancerous and normal cells. Phys Rev E Stat Nonlinear Soft Matter Phys 92(6):062702

    Google Scholar 

  136. Jonsson MK, Wang QD, Becker B (2011) Impedance-based detection of beating rhythm and proarrhythmic effects of compounds on stem cell-derived cardiomyocytes. Assay Drug Dev Technol 9(6):589–599

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Guo L, Abrams RM, Babiarz JE, Cohen JD, Kameoka S, Sanders MJ, Chiao E, Kolaja KL (2011) Estimating the risk of drug-induced proarrhythmia using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci 123(1):281–289

    CAS  PubMed  Google Scholar 

  138. Lamore SD, Kamendi HW, Scott CW, Dragan YP, Peters MF (2013) Cellular impedance assays for predictive preclinical drug screening of kinase inhibitor cardiovascular toxicity. Toxicol Sci 135(2):402–413

    CAS  PubMed  Google Scholar 

  139. Scott CW, Zhang X, Abi-Gerges N, Lamore SD, Abassi YA, Peters MF (2014) An impedance-based cellular assay using human iPSC-derived cardiomyocytes to quantify modulators of cardiac contractility. Toxicol Sci 142(2):331–338

    CAS  PubMed  Google Scholar 

  140. Kramer N, Walzl A, Unger C, Rosner M, Krupitza G, Hengstschlager M, Dolznig H (2013) In vitro cell migration and invasion assays. Mutat Res 752(1):10–24

    CAS  PubMed  Google Scholar 

  141. Renken C, Keese C, Giaever I (2010) Automated assays for quantifying cell migration. Biotechniques 49(5):844

    CAS  Google Scholar 

  142. Desai SD, Reed RE, Burks J, Wood LM, Pullikuth AK, Haas AL, Liu LF, Breslin JW, Meiners S, Sankar S (2012) ISG15 disrupts cytoskeletal architecture and promotes motility in human breast cancer cells. Exp Biol Med 237(1):38–49

    CAS  Google Scholar 

  143. Jiang WG, Martin TA, Lewis-Russell JM, Douglas-Jones A, Ye L, Mansel RE (2008) Eplin-alpha expression in human breast cancer, the impact on cellular migration and clinical outcome. Mol Cancer 7:71

    PubMed  PubMed Central  Google Scholar 

  144. Kim SH, Nagalingam A, Saxena NK, Singh SV, Sharma D (2011) Benzyl isothiocyanate inhibits oncogenic actions of leptin in human breast cancer cells by suppressing activation of signal transducer and activator of transcription 3. Carcinogenesis 32(3):359–367

    PubMed  Google Scholar 

  145. Knight BB, Oprea-Ilies GM, Nagalingam A, Yang L, Cohen C, Saxena NK, Sharma D (2011) Surviving upregulation, dependent on leptin-EGFR-Notch1 axis, is essential for leptin-induced migration of breast carcinoma cells. Endocr Relat Cancer 18(4):413–428

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Nagalingam A, Arbiser JL, Bonner MY, Saxena NK, Sharma D (2012) Honokiol activates AMP-activated protein kinase in breast cancer cells via an LKB1-dependent pathway and inhibits breast carcinogenesis. Breast Cancer Res 14(1):R35

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Sun PH, Ye L, Mason MD, Jiang WG (2012) Protein tyrosine phosphatase micro (PTP micro or PTPRM), a negative regulator of proliferation and invasion of breast cancer cells, is associated with disease prognosis. PLoS One 7(11):e50183

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Yan T, Skaftnesmo KO, Leiss L, Sleire L, Wang J, Li X, Enger PO (2011) Neuronal markers are expressed in human gliomas and NSE knockdown sensitizes glioblastoma cells to radiotherapy and temozolomide. BMC Cancer 11:524

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Zhang N, Sanders AJ, Ye L, Kynaston HG, Jiang WG (2010) Expression of vascular endothelial growth inhibitor (VEGI) in human urothelial cancer of the bladder and its effects on the adhesion and migration of bladder cancer cells in vitro. Anticancer Res 30(1):87–95

    CAS  PubMed  Google Scholar 

  150. Allen-Gipson DS, Zimmerman MC, Zhang H, Castellanos G, O’Malley JK, Alvarez-Ramirez H, Kharbanda K, Sisson JH, Wyatt TA (2013) Smoke extract impairs adenosine wound healing: implications of smoke-generated reactive oxygen species. Am J Respir Cell Mol Biol 48(5):665–673

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Bosanquet DC, Harding KG, Ruge F, Sanders AJ, Jiang WG (2012) Expression of IL-24 and IL-24 receptors in human wound tissues and the biological implications of IL-24 on keratinocytes. Wound Repair Regen 20(6):896–903

    PubMed  Google Scholar 

  152. Bosanquet DC, Ye L, Harding KG, Jiang WG (2012) Role of HuR in keratinocyte migration and wound healing. Mol Med Rep 5(2):529–534

    CAS  PubMed  Google Scholar 

  153. Charrier L, Yan Y, Driss A, Laboisse CL, Sitaraman SV, Merlin D (2005) ADAM-15 inhibits wound healing in human intestinal epithelial cell monolayers. Am J Physiol Gastrointest Liver Physiol 288(2):G346–G353

    CAS  PubMed  Google Scholar 

  154. Heijink IH, Brandenburg SM, Postma DS, van Oosterhout AJ (2012) Cigarette smoke impairs airway epithelial barrier function and cell-cell contact recovery. Eur Respir J 39(2):419–428

    CAS  PubMed  Google Scholar 

  155. Hsu CC, Tsai WC, Chen CP, Lu YM, Wang JS (2010) Effects of negative pressures on epithelial tight junctions and migration in wound healing. Am J Physiol Cell Physiol 299(2):C528–C534

    CAS  PubMed  Google Scholar 

  156. Itokazu Y, Pagano RE, Schroeder AS, O’Grady SM, Limper AH, Marks DL (2014) Reduced GM1 ganglioside in CFTR-deficient human airway cells results in decreased beta1-integrin signaling and delayed wound repair. Am J Physiol Cell Physiol 306(9):C819–C830

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Jiang WG, Sanders AJ, Ruge F, Harding KG (2012) Influence of interleukin-8 (IL-8) and IL-8 receptors on the migration of human keratinocytes, the role of PLC-γ and potential clinical implications. Exp Ther Med 3(2):231–236

    CAS  PubMed  Google Scholar 

  158. Jiang WG, Ye L, Patel G, Harding KG (2010) Expression of WAVEs, the WASP (Wiskott-Aldrich syndrome protein) family of verprolin homologous proteins in human wound tissues and the biological influence on human keratinocytes. Wound Repair Regen 18(6):594–604

    PubMed  Google Scholar 

  159. Oudhoff MJ, Kroeze KL, Nazmi K, van den Keijbus PA, van’t Hof W, Fernandez-Borja M, Hordijk PL, Gibbs S, Bolscher JG, Veerman EC (2009) Structure-activity analysis of histatin, a potent wound healing peptide from human saliva: cyclization of histatin potentiates molar activity 1,000-fold. FASEB J 23(11):3928–3935

    CAS  PubMed  Google Scholar 

  160. Sanders AJ, Jiang DG, Jiang WG, Harding KG, Patel GK (2011) Activated leukocyte cell adhesion molecule impacts on clinical wound healing and inhibits HaCaT migration. Int Wound J 8(5):500–507

    PubMed  PubMed Central  Google Scholar 

  161. Mehta RR, Yamada T, Taylor BN, Christov K, King ML, Majumdar D, Lekmine F, Tiruppathi C, Shilkaitis A, Bratescu L, Green A, Beattie CW, Das Gupta TK (2011) A cell penetrating peptide derived from azurin inhibits angiogenesis and tumor growth by inhibiting phosphorylation of VEGFR-2, FAK and Akt. Angiogenesis 14(3):355–369

    CAS  PubMed  Google Scholar 

  162. Ungvari Z, Tucsek Z, Sosnowska D, Toth P, Gautam T, Podlutsky A, Csiszar A, Losonczy G, Valcarcel-Ares MN, Sonntag WE, Csiszar A (2013) Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells. J Gerontol A Biol Sci Med Sci 68(8):877–891

    CAS  PubMed  Google Scholar 

  163. Chanakira A, Kir D, Barke RA, Santilli SM, Ramakrishnan S, Roy S (2015) Hypoxia differentially regulates arterial and venous smooth muscle cell migration. PLoS One 10(9):e0138587

    PubMed  PubMed Central  Google Scholar 

  164. Tsapara A, Luthert P, Greenwood J, Hill CS, Matter K, Balda MS (2010) The RhoA activator GEF-H1/Lfc is a transforming growth factor-beta target gene and effector that regulates alpha-smooth muscle actin expression and cell migration. Mol Biol Cell 21(6):860–870

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Hughes CS, Postovit LM, Lajoie GA (2010) Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10(9):1886–1890

    CAS  PubMed  Google Scholar 

  166. Chung H, Suh EK, Han IO, Oh ES (2011) Keratinocyte-derived laminin-332 promotes adhesion and migration in melanocytes and melanoma. J Biol Chem 286(15):13438–13447

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Coutts AS, Pires IM, Weston L, Buffa FM, Milani M, Li JL, Harris AL, Hammond EM, La Thangue NB (2011) Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1alpha. Oncogene 30(48):4835–4842

    CAS  PubMed  Google Scholar 

  168. Daouti S, Li WH, Qian H, Huang KS, Holmgren J, Levin W, Reik L, McGady DL, Gillespie P, Perrotta A, Bian H, Reidhaar-Olson JF, Bliss SA, Olivier AR, Sergi JA, Fry D, Danho W, Ritland S, Fotouhi N, Heimbrook D, Niu H (2008) A selective phosphatase of regenerating liver phosphatase inhibitor suppresses tumor cell anchorage-independent growth by a novel mechanism involving p130Cas cleavage. Cancer Res 68(4):1162–1169

    CAS  PubMed  Google Scholar 

  169. Arabzadeh A, Dupaul-Chicoine J, Breton V, Haftchenary S, Yumeen S, Turbide C, Saleh M, McGregor K, Greenwood CM, Akavia UD, Blumberg RS, Gunning PT, Beauchemin N (2016) Carcinoembryonic Antigen Cell Adhesion Molecule 1 long isoform modulates malignancy of poorly differentiated colon cancer cells. Gut 65(5):821–829

    CAS  PubMed  Google Scholar 

  170. Grassilli S, Brugnoli F, Lattanzio R, Rossi C, Perracchio L, Mottolese M, Marchisio M, Palomba M, Nika E, Natali PG, Piantelli M, Capitani S, Bertagnolo V (2014) High nuclear level of Vav1 is a positive prognostic factor in early invasive breast tumors: a role in modulating genes related to the efficiency of metastatic process. Oncotarget 5(12):4320–4336

    PubMed  PubMed Central  Google Scholar 

  171. Burlacu A, Grigorescu G, Rosca A-M, Preda MB, Simionescu M (2012) Factors secreted by mesenchymal stem cells and endothelial progenitor cells have complementary effects on angiogenesis in vitro. Stem Cells Dev 22(4):643–653

    PubMed  PubMed Central  Google Scholar 

  172. Rutten MJ, Laraway B, Gregory CR, Xie H, Renken C, Keese C, Gregory KW (2015) Rapid assay of stem cell functionality and potency using electric cell-substrate impedance sensing. Stem Cell Res Ther 6:192

    PubMed  PubMed Central  Google Scholar 

  173. Neubig RR, Spedding M, Kenakin T, Christopoulos A, International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (2003) International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev 55(4):597–606

    CAS  PubMed  Google Scholar 

  174. Stolwijk JA, Zhang X, Gueguinou M, Zhang W, Matrougui K, Renken C, Trebak M (2016) Calcium signaling is dispensable for receptor-regulation of endothelial barrier function. J Biol Chem 291(44):22894–22912

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Urban C, Hamacher A, Partke HJ, Roden M, Schinner S, Christiansen E, Due-Hansen ME, Ulven T, Gohlke H, Kassack MU (2013) In vitro and mouse in vivo characterization of the potent free fatty acid 1 receptor agonist TUG-469. Naunyn Schmiedebergs Arch Pharmacol 386(12):1021–1030

    CAS  PubMed  Google Scholar 

  176. Guo D, Mulder-Krieger T, IJzerman AP, Heitman LH (2012) Functional efficacy of adenosine A(2)A receptor agonists is positively correlated to their receptor residence time. Br J Pharmacol 166(6):1846–1859

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Lu Q, Harrington EO, Newton J, Casserly B, Radin G, Warburton R, Zhou Y, Blackburn MR, Rounds S (2010) Adenosine protected against pulmonary edema through transporter- and receptor A2-mediated endothelial barrier enhancement. Am J Physiol Lung Cell Mol Physiol 298(6):L755–L767

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Anthony DF, Sin YY, Vadrevu S, Advant N, Day JP, Byrne AM, Lynch MJ, Milligan G, Houslay MD, Baillie GS (2011) β-Arrestin 1 inhibits the GTPase-activating protein function of ARHGAP21, promoting activation of RhoA following angiotensin II type 1A receptor stimulation. Mol Cell Biol 31(5):1066–1075

    CAS  PubMed  Google Scholar 

  179. Denelavas A, Weibel F, Prummer M, Imbach A, Clerc RG, Apfel CM, Hertel C (2011) Real-time cellular impedance measurements detect Ca(2+) channel-dependent oscillations of morphology in human H295R adrenoma cells. Biochim Biophys Acta 1813(5):754–762

    CAS  PubMed  Google Scholar 

  180. Peitzman ER, Zaidman NA, Maniak PJ, O’Grady SM (2015) Agonist binding to beta-adrenergic receptors on human airway epithelial cells inhibits migration and wound repair. Am J Physiol Cell Physiol 309(12):C847–C855

    CAS  PubMed  PubMed Central  Google Scholar 

  181. Wegener J, Zink S, Rosen P, Galla H (1999) Use of electrochemical impedance measurements to monitor beta-adrenergic stimulation of bovine aortic endothelial cells. Pflugers Arch 437(6):925–934

    CAS  PubMed  Google Scholar 

  182. Watts AO, Scholten DJ, Heitman LH, Vischer HF, Leurs R (2012) Label-free impedance responses of endogenous and synthetic chemokine receptor CXCR3 agonists correlate with Gi-protein pathway activation. Biochem Biophys Res Commun 419(2):412–418

    CAS  PubMed  Google Scholar 

  183. Adderley SP, Zhang XE, Breslin JW (2015) Involvement of the H1 histamine receptor, p38 MAP kinase, myosin light chains kinase, and Rho/ROCK in histamine-induced endothelial barrier dysfunction. Microcirculation 22(4):237–248

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Lieb S, Littmann T, Plank N, Felixberger J, Tanaka M, Schafer T, Krief S, Elz S, Friedland K, Bernhardt G, Wegener J, Ozawa T, Buschauer A (2016) Label-free versus conventional cellular assays: functional investigations on the human histamine H1 receptor. Pharmacol Res 114:13–26

    CAS  PubMed  Google Scholar 

  185. Stolwijk JA, Skiba M, Kade C, Bernhardt G, Buschauer A, Hubner H, Gmeiner P, Wegener J (2019) Increasing the throughput of label-free cell assays to study the activation of G-protein-coupled receptors by using a serial agonist exposure protocol. Integr Biol. https://doi.org/10.1093/intbio/zyz010

    Google Scholar 

  186. Zhang X, Tan F, Brovkovych V, Zhang Y, Skidgel RA (2011) Cross-talk between carboxypeptidase M and the kinin B1 receptor mediates a new mode of G protein-coupled receptor signaling. J Biol Chem 286(21):18547–18561

    CAS  PubMed  PubMed Central  Google Scholar 

  187. He D, Su Y, Usatyuk PV, Spannhake EW, Kogut P, Solway J, Natarajan V, Zhao Y (2009) Lysophosphatidic acid enhances pulmonary epithelial barrier integrity and protects endotoxin-induced epithelial barrier disruption and lung injury. J Biol Chem 284(36):24123–24132

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Qiao J, Huang F, Naikawadi RP, Kim KS, Said T, Lum H (2006) Lysophosphatidylcholine impairs endothelial barrier function through the G protein-coupled receptor GPR4. Am J Physiol Lung Cell Mol Physiol 291(1):L91–L101

    CAS  PubMed  Google Scholar 

  189. Kammermann M, Denelavas A, Imbach A, Grether U, Dehmlow H, Apfel CM, Hertel C (2011) Impedance measurement: a new method to detect ligand-biased receptor signaling. Biochem Biophys Res Commun 412(3):419–424

    CAS  PubMed  Google Scholar 

  190. Meshki J, Douglas SD, Lai JP, Schwartz L, Kilpatrick LE, Tuluc F (2009) Neurokinin 1 receptor mediates membrane blebbing in HEK293 cells through a Rho/Rho-associated coiled-coil kinase-dependent mechanism. J Biol Chem 284(14):9280–9289

    CAS  PubMed  PubMed Central  Google Scholar 

  191. Srivastava SK, Ramaneti R, Roelse M, Tong HD, Vrouwe EX, Brinkman AG, de Smet LC, van Rijn CJ, Jongsma MA (2015) A generic microfluidic biosensor of G protein-coupled receptor activation–impedance measurements of reversible morphological changes of reverse transfected HEK293 cells on microelectrodes. RSC Adv 5(65):52563–52570

    CAS  Google Scholar 

  192. Reddy L, Wang HS, Keese CR, Giaever I, Smith TJ (1998) Assessment of rapid morphological changes associated with elevated cAMP levels in human orbital fibroblasts. Exp Cell Res 245(2):360–367

    CAS  PubMed  Google Scholar 

  193. Smith TJ, Wang HS, Hogg MG, Henrikson RC, Keese CR, Giaever I (1994) Prostaglandin E2 elicits a morphological change in cultured orbital fibroblasts from patients with Graves ophthalmopathy. Proc Natl Acad Sci U S A 91(11):5094–5098

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Wang H, Keese CR, Giaever I, Smith TJ (1995) Prostaglandin E2 alters human orbital fibroblast shape through a mechanism involving the generation of cyclic adenosine monophosphate. J Clin Endocrinol Metab 80(12):3553–3560

    CAS  PubMed  Google Scholar 

  195. Argraves KM, Gazzolo PJ, Groh EM, Wilkerson BA, Matsuura BS, Twal WO, Hammad SM, Argraves WS (2008) High density lipoprotein-associated sphingosine 1-phosphate promotes endothelial barrier function. J Biol Chem 283(36):25074–25081

    CAS  PubMed  PubMed Central  Google Scholar 

  196. Garcia JG, Liu F, Verin AD, Birukova A, Dechert MA, Gerthoffer WT, Bamberg JR, English D (2001) Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J Clin Invest 108(5):689–701

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Schaphorst KL, Chiang E, Jacobs KN, Zaiman A, Natarajan V, Wigley F, Garcia JG (2003) Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products. Am J Physiol Lung Cell Mol Physiol 285(1):L258–L267

    CAS  PubMed  Google Scholar 

  198. Wilkerson BA, Grass GD, Wing SB, Argraves WS, Argraves KM (2012) Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endothelial barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier enhancement as compared with albumin-S1P via effects on levels, trafficking, and signaling of S1P1. J Biol Chem 287(53):44645–44653

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Becker PM, Verin AD, Booth MA, Liu F, Birukova A, Garcia JG (2001) Differential regulation of diverse physiological responses to VEGF in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol 281(6):L1500–L1511

    CAS  PubMed  Google Scholar 

  200. Birukova AA, Cokic I, Moldobaeva N, Birukov KG (2009) Paxillin is involved in the differential regulation of endothelial barrier by HGF and VEGF. Am J Respir Cell Mol Biol 40(1):99–107

    CAS  PubMed  Google Scholar 

  201. Ngok SP, Geyer R, Liu M, Kourtidis A, Agrawal S, Wu C, Seerapu HR, Lewis-Tuffin LJ, Moodie KL, Huveldt D, Marx R, Baraban JM, Storz P, Horowitz A, Anastasiadis PZ (2012) VEGF and Angiopoietin-1 exert opposing effects on cell junctions by regulating the Rho GEF Syx. J Cell Biol 199(7):1103–1115

    CAS  PubMed  PubMed Central  Google Scholar 

  202. Sahin O, Frohlich H, Lobke C, Korf U, Burmester S, Majety M, Mattern J, Schupp I, Chaouiya C, Thieffry D, Poustka A, Wiemann S, Beissbarth T, Arlt D (2009) Modeling ERBB receptor-regulated G1/S transition to find novel targets for de novo trastuzumab resistance. BMC Syst Biol 3:1

    PubMed  PubMed Central  Google Scholar 

  203. Takahashi N, Seko Y, Noiri E, Tobe K, Kadowaki T, Sabe H, Yazaki Y (1999) Vascular endothelial growth factor induces activation and subcellular translocation of focal adhesion kinase (p125FAK) in cultured rat cardiac myocytes. Circ Res 84(10):1194–1202

    CAS  PubMed  Google Scholar 

  204. Xue M, Chow SO, Dervish S, Chan YK, Julovi SM, Jackson CJ (2011) Activated protein C enhances human keratinocyte barrier integrity via sequential activation of epidermal growth factor receptor and Tie2. J Biol Chem 286(8):6742–6750

    CAS  PubMed  Google Scholar 

  205. Yang J, Duh EJ, Caldwell RB, Behzadian MA (2010) Antipermeability function of PEDF involves blockade of the MAP kinase/GSK/beta-catenin signaling pathway and uPAR expression. Invest Ophthalmol Vis Sci 51(6):3273–3280

    PubMed  PubMed Central  Google Scholar 

  206. Clark PR, Kim RK, Pober JS, Kluger MS (2015) Tumor necrosis factor disrupts claudin-5 endothelial tight junction barriers in two distinct NF-kappaB-dependent phases. PLoS One 10(3):e0120075

    PubMed  PubMed Central  Google Scholar 

  207. Haines RJ, Beard Jr RS, Wu MH (2015) Protein tyrosine kinase 6 mediates TNFalpha-induced endothelial barrier dysfunction. Biochem Biophys Res Commun 456(1):190–196

    CAS  PubMed  Google Scholar 

  208. Kakiashvili E, Dan Q, Vandermeer M, Zhang Y, Waheed F, Pham M, Szaszi K (2011) The epidermal growth factor receptor mediates tumor necrosis factor-alpha-induced activation of the ERK/GEF-H1/RhoA pathway in tubular epithelium. J Biol Chem 286(11):9268–9279

    CAS  PubMed  PubMed Central  Google Scholar 

  209. Pathak RR, Grover A, Malaney P, Quarni W, Pandit A, Allen-Gipson D, Dave V (2013) Loss of phosphatase and tensin homolog (PTEN) induces leptin-mediated leptin gene expression: feed-forward loop operating in the lung. J Biol Chem 288(41):29821–29835

    CAS  PubMed  PubMed Central  Google Scholar 

  210. Piegeler T, Votta-Velis EG, Bakhshi FR, Mao M, Carnegie G, Bonini MG, Schwartz DE, Borgeat A, Beck-Schimmer B, Minshall RD (2014) Endothelial barrier protection by local anesthetics: ropivacaine and lidocaine block tumor necrosis factor-alpha-induced endothelial cell Src activation. Anesthesiology 120(6):1414–1428

    CAS  PubMed  Google Scholar 

  211. Rigor RR, Beard Jr RS, Litovka OP, Yuan SY (2012) Interleukin-1beta-induced barrier dysfunction is signaled through PKC-theta in human brain microvascular endothelium. Am J Physiol Cell Physiol 302(10):C1513–C1522

    CAS  PubMed  Google Scholar 

  212. Birukova AA, Xing J, Fu P, Yakubov B, Dubrovskyi O, Fortune JA, Klibanov AM, Birukov KG (2010) Atrial natriuretic peptide attenuates LPS-induced lung vascular leak: role of PAK1. Am J Physiol Lung Cell Mol Physiol 299(5):L652–L663

    CAS  PubMed  PubMed Central  Google Scholar 

  213. Joshi AD, Dimitropoulou C, Thangjam G, Snead C, Feldman S, Barabutis N, Fulton D, Hou Y, Kumar S, Patel V, Gorshkov B, Verin AD, Black SM, Catravas JD (2014) Heat shock protein 90 inhibitors prevent LPS-induced endothelial barrier dysfunction by disrupting RhoA signaling. Am J Respir Cell Mol Biol 50(1):170–179

    CAS  PubMed  PubMed Central  Google Scholar 

  214. Clements RT, Minnear FL, Singer HA, Keller RS, Vincent PA (2005) RhoA and Rho-kinase dependent and independent signals mediate TGF-beta-induced pulmonary endothelial cytoskeletal reorganization and permeability. Am J Physiol Lung Cell Mol Physiol 288(2):L294–L306

    CAS  PubMed  Google Scholar 

  215. Goldberg PL, MacNaughton DE, Clements RT, Minnear FL, Vincent PA (2002) p38 MAPK activation by TGF-beta1 increases MLC phosphorylation and endothelial monolayer permeability. Am J Physiol Lung Cell Mol Physiol 282(1):L146–L154

    CAS  PubMed  Google Scholar 

  216. Sung JY, Park SY, Kim JH, Kang HG, Yoon JH, Na YS, Kim YN, Park BK (2014) Interferon consensus sequence-binding protein (ICSBP) promotes epithelial-to-mesenchymal transition (EMT)-like phenomena, cell-motility, and invasion via TGF-beta signaling in U2OS cells. Cell Death Dis 5:e1224

    CAS  PubMed  PubMed Central  Google Scholar 

  217. O’Donnell EF, Kopparapu PR, Koch DC, Jang HS, Phillips JL, Tanguay RL, Kerkvliet NI, Kolluri SK (2012) The aryl hydrocarbon receptor mediates leflunomide-induced growth inhibition of melanoma cells. PLoS One 7(7):e40926

    PubMed  PubMed Central  Google Scholar 

  218. Rotroff DM, Dix DJ, Houck KA, Kavlock RJ, Knudsen TB, Martin MT, Reif DM, Richard AM, Sipes NS, Abassi YA, Jin C, Stampfl M, Judson RS (2013) Real-time growth kinetics measuring hormone mimicry for ToxCast chemicals in T-47D human ductal carcinoma cells. Chem Res Toxicol 26(7):1097–1107

    CAS  PubMed  Google Scholar 

  219. Tian J, Smith A, Nechtman J, Podolsky R, Aggarwal S, Snead C, Kumar S, Elgaish M, Oishi P, Goerlach A, Fratz S, Hess J, Catravas JD, Verin AD, Fineman JR, She JX, Black SM (2009) Effect of PPARgamma inhibition on pulmonary endothelial cell gene expression: gene profiling in pulmonary hypertension. Physiol Genomics 40(1):48–60

    CAS  PubMed  PubMed Central  Google Scholar 

  220. Wolfson RK, Chiang ET, Garcia JG (2011) HMGB1 induces human lung endothelial cell cytoskeletal rearrangement and barrier disruption. Microvasc Res 81(2):189–197

    CAS  PubMed  Google Scholar 

  221. Yuan L, Le Bras A, Sacharidou A, Itagaki K, Zhan Y, Kondo M, Carman CV, Davis GE, Aird WC, Oettgen P (2012) ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene. J Biol Chem 287(9):6582–6591

    CAS  PubMed  PubMed Central  Google Scholar 

  222. Privratsky JR, Paddock CM, Florey O, Newman DK, Muller WA, Newman PJ (2011) Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity. J Cell Sci 124(Pt 9):1477–1485

    CAS  PubMed  PubMed Central  Google Scholar 

  223. Sun C, Wu MH, Guo M, Day ML, Lee ES, Yuan SY (2010) ADAM15 regulates endothelial permeability and neutrophil migration via Src/ERK1/2 signalling. Cardiovasc Res 87(2):348–355

    CAS  PubMed  PubMed Central  Google Scholar 

  224. van Wetering S, van den Berk N, van Buul JD, Mul FP, Lommerse I, Mous R, ten Klooster JP, Zwaginga JJ, Hordijk PL (2003) VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration. Am J Physiol Cell Physiol 285(2):C343–C352

    PubMed  Google Scholar 

  225. Peters MF, Vaillancourt F, Heroux M, Valiquette M, Scott CW (2010) Comparing label-free biosensors for pharmacological screening with cell-based functional assays. Assay Drug Dev Technol 8(2):219–227

    CAS  PubMed  Google Scholar 

  226. Gainor JP, Morton CA, Roberts JT, Vincent PA, Minnear FL (2001) Platelet-conditioned medium increases endothelial electrical resistance independently of cAMP/PKA and cGMP/PKG. Am J Physiol Heart Circ Physiol 281(5):H1992–H2001

    CAS  PubMed  Google Scholar 

  227. Halai R, Croker DE, Suen JY, Fairlie DP, Cooper MA (2012) A comparative study of impedance versus optical label-free systems relative to labelled assays in a predominantly Gi coupled GPCR (C5aR) signalling. Biosensors 2(3):273–290

    CAS  PubMed  PubMed Central  Google Scholar 

  228. Konya V, Ullen A, Kampitsch N, Theiler A, Philipose S, Parzmair GP, Marsche G, Peskar BA, Schuligoi R, Sattler W, Heinemann A (2013) Endothelial E-type prostanoid 4 receptors promote barrier function and inhibit neutrophil trafficking. J Allergy Clin Immunol 131(2):532–540.e1-2

    CAS  PubMed  Google Scholar 

  229. Atienza JM, Yu N, Wang X, Xu X, Abassi Y (2006) Label-free and real-time cell-based kinase assay for screening selective and potent receptor tyrosine kinase inhibitors using microelectronic sensor array. J Biomol Screen 11(6):634–643

    CAS  PubMed  Google Scholar 

  230. Xu M, Waters CL, Hu C, Wysolmerski RB, Vincent PA, Minnear FL (2007) Sphingosine 1-phosphate rapidly increases endothelial barrier function independently of VE-cadherin but requires cell spreading and Rho kinase. Am J Physiol Cell Physiol 293(4):C1309–C1318

    CAS  PubMed  Google Scholar 

  231. Huang F, Subbaiah PV, Holian O, Zhang J, Johnson A, Gertzberg N, Lum H (2005) Lysophosphatidylcholine increases endothelial permeability: role of PKCalpha and RhoA cross talk. Am J Physiol Lung Cell Mol Physiol 289(2):L176–L185

    CAS  PubMed  Google Scholar 

  232. McLaughlin JN, Shen L, Holinstat M, Brooks JD, Dibenedetto E, Hamm HE (2005) Functional selectivity of G protein signaling by agonist peptides and thrombin for the protease-activated receptor-1. J Biol Chem 280(26):25048–25059

    CAS  PubMed  Google Scholar 

  233. Minshall RD, Vandenbroucke EE, Holinstat M, Place AT, Tiruppathi C, Vogel SM, van Nieuw Amerongen GP, Mehta D, Malik AB (2010) Role of protein kinase Czeta in thrombin-induced RhoA activation and inter-endothelial gap formation of human dermal microvessel endothelial cell monolayers. Microvasc Res 80(2):240–249

    CAS  PubMed  PubMed Central  Google Scholar 

  234. Stallaert W, Dorn JF, van der Westhuizen E, Audet M, Bouvier M (2012) Impedance responses reveal beta(2)-adrenergic receptor signaling pluridimensionality and allow classification of ligands with distinct signaling profiles. PLoS One 7(1):e29420

    CAS  PubMed  PubMed Central  Google Scholar 

  235. Zhang XE, Adderley SP, Breslin JW (2016) Activation of RhoA, but not Rac1, mediates early stages of S1P-induced endothelial barrier enhancement. PLoS One 11(5):e0155490

    PubMed  PubMed Central  Google Scholar 

  236. Ji J, Jia S, Jia Y, Ji K, Hargest R, Jiang WG (2015) WISP-2 in human gastric cancer and its potential metastatic suppressor role in gastric cancer cells mediated by JNK and PLC-gamma pathways. Br J Cancer 113(6):921–933

    CAS  PubMed  PubMed Central  Google Scholar 

  237. Liu S, Yu C, Yang F, Paganini-Hill A, Fisher MJ (2012) Phosphodiesterase inhibitor modulation of brain microvascular endothelial cell barrier properties. J Neurol Sci 320(1–2):45–51

    CAS  PubMed  PubMed Central  Google Scholar 

  238. Shinde AV, Motiani RK, Zhang X, Abdullaev IF, Adam AP, Gonzalez-Cobos JC, Zhang W, Matrougui K, Vincent PA, Trebak M (2013) STIM1 controls endothelial barrier function independently of Orai1 and Ca2+ entry. Sci Signal 6(267):ra18

    PubMed  PubMed Central  Google Scholar 

  239. Lorenowicz MJ, Fernandez-Borja M, Kooistra MR, Bos JL, Hordijk PL (2008) PKA and Epac1 regulate endothelial integrity and migration through parallel and independent pathways. Eur J Cell Biol 87(10):779–792

    CAS  PubMed  Google Scholar 

  240. Moldobaeva A, Welsh-Servinsky LE, Shimoda LA, Stephens RS, Verin AD, Tuder RM, Pearse DB (2006) Role of protein kinase G in barrier-protective effects of cGMP in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 290(5):L919–L930

    CAS  PubMed  Google Scholar 

  241. Adyshev DM, Dudek SM, Moldobaeva N, Kim KM, Ma SF, Kasa A, Garcia JG, Verin AD (2013) Ezrin/radixin/moesin proteins differentially regulate endothelial hyperpermeability after thrombin. Am J Physiol Lung Cell Mol Physiol 305(3):L240–L255

    CAS  PubMed  PubMed Central  Google Scholar 

  242. Birukova AA, Birukov KG, Smurova K, Adyshev D, Kaibuchi K, Alieva I, Garcia JG, Verin AD (2004) Novel role of microtubules in thrombin-induced endothelial barrier dysfunction. FASEB J 18(15):1879–1890

    CAS  PubMed  Google Scholar 

  243. Rentsendorj O, Mirzapoiazova T, Adyshev D, Servinsky LE, Renne T, Verin AD, Pearse DB (2008) Role of vasodilator-stimulated phosphoprotein in cGMP-mediated protection of human pulmonary artery endothelial barrier function. Am J Physiol Lung Cell Mol Physiol 294(4):L686–L697

    CAS  PubMed  Google Scholar 

  244. Escudero-Esparza A, Jiang WG, Martin TA (2012) Claudin-5 participates in the regulation of endothelial cell motility. Mol Cell Biochem 362(1–2):71–85

    CAS  PubMed  Google Scholar 

  245. Finigan JH, Dudek SM, Singleton PA, Chiang ET, Jacobson JR, Camp SM, Ye SQ, Garcia JG (2005) Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation. J Biol Chem 280(17):17286–17293

    CAS  PubMed  Google Scholar 

  246. Grinnell KL, Chichger H, Braza J, Duong H, Harrington EO (2012) Protection against LPS-induced pulmonary edema through the attenuation of protein tyrosine phosphatase-1B oxidation. Am J Respir Cell Mol Biol 46(5):623–632

    CAS  PubMed  PubMed Central  Google Scholar 

  247. Sun C, Wu MH, Yuan SY (2011) Nonmuscle myosin light-chain kinase deficiency attenuates atherosclerosis in apolipoprotein E–deficient mice via reduced endothelial barrier dysfunction and monocyte migration. Circulation 124(1):48–57

    CAS  PubMed  PubMed Central  Google Scholar 

  248. Herron CR, Lowery AM, Hollister PR, Reynolds AB, Vincent PA (2011) p120 regulates endothelial permeability independently of its NH2 terminus and Rho binding. Am J Physiol Heart Circ Physiol 300(1):H36–H48

    CAS  PubMed  Google Scholar 

  249. Sawhney RS, Liu W, Brattain MG (2009) A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via Fak signaling. J Cell Physiol 219(1):152–161

    CAS  PubMed  PubMed Central  Google Scholar 

  250. Bilir B, Kucuk O, Moreno CS (2013) Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells. J Transl Med 11:280

    PubMed  PubMed Central  Google Scholar 

  251. Wilson JL, Taylor L, Polgar P (2012) Endothelin-1 activation of ETB receptors leads to a reduced cellular proliferative rate and an increased cellular footprint. Exp Cell Res 318(10):1125–1133

    CAS  PubMed  PubMed Central  Google Scholar 

  252. Yuan L, Zhang H, Liu J, Rubin JB, Cho YJ, Shu HK, Schniederjan M, MacDonald TJ (2013) Growth factor receptor-Src-mediated suppression of GRK6 dysregulates CXCR4 signaling and promotes medulloblastoma migration. Mol Cancer 12:18

    CAS  PubMed  PubMed Central  Google Scholar 

  253. Berdyshev EV, Gorshkova IA, Usatyuk P, Zhao Y, Saatian B, Hubbard W, Natarajan V (2006) De novo biosynthesis of dihydrosphingosine-1-phosphate by sphingosine kinase 1 in mammalian cells. Cell Signal 18(10):1779–1792

    CAS  PubMed  Google Scholar 

  254. Rask-Andersen M, Almen MS, Schioth HB (2011) Trends in the exploitation of novel drug targets. Nat Rev Drug Discov 10(8):579–590

    CAS  PubMed  Google Scholar 

  255. Hoffman BB, Lefkowitz RJ (1980) Radioligand binding studies of adrenergic receptors: new insights into molecular and physiological regulation. Annu Rev Pharmacol Toxicol 20:581–608

    CAS  PubMed  Google Scholar 

  256. Maguire JJ, Kuc RE, Davenport AP (2012) Radioligand binding assays and their analysis. Methods Mol Biol 897:31–77

    CAS  PubMed  Google Scholar 

  257. Kenakin TP (2009) Cellular assays as portals to seven-transmembrane receptor-based drug discovery. Nat Rev Drug Discov 8(8):617–626

    CAS  PubMed  Google Scholar 

  258. Thomsen W, Frazer J, Unett D (2005) Functional assays for screening GPCR targets. Curr Opin Biotechnol 16(6):655–665

    CAS  PubMed  Google Scholar 

  259. Zhang R, Xie X (2012) Tools for GPCR drug discovery. Acta Pharmacol Sin 33(3):372–384

    CAS  PubMed  PubMed Central  Google Scholar 

  260. Cooper MA (2003) Label-free screening of bio-molecular interactions. Anal Bioanal Chem 377(5):834–842

    CAS  PubMed  Google Scholar 

  261. Fang Y (2014) Label-free drug discovery. Front Pharmacol 5:52

    PubMed  PubMed Central  Google Scholar 

  262. McGuinness R (2007) Impedance-based cellular assay technologies: recent advances, future promise. Curr Opin Pharmacol 7(5):535–540

    CAS  PubMed  Google Scholar 

  263. Miyano K, Sudo Y, Yokoyama A, Hisaoka-Nakashima K, Morioka N, Takebayashi M, Nakata Y, Higami Y, Uezono Y (2014) History of the G protein-coupled receptor (GPCR) assays from traditional to a state-of-the-art biosensor assay. J Pharmacol Sci 126(4):302–309

    CAS  PubMed  Google Scholar 

  264. Peters MF, Scott CW (2009) Evaluating cellular impedance assays for detection of GPCR pleiotropic signaling and functional selectivity. J Biomol Screen 14(3):246–255

    CAS  PubMed  Google Scholar 

  265. Schroder R, Schmidt J, Blattermann S, Peters L, Janssen N, Grundmann M, Seemann W, Kaufel D, Merten N, Drewke C, Gomeza J, Milligan G, Mohr K, Kostenis E (2011) Applying label-free dynamic mass redistribution technology to frame signaling of G protein-coupled receptors noninvasively in living cells. Nat Protoc 6(11):1748–1760

    PubMed  Google Scholar 

  266. Scott CW, Peters MF (2010) Label-free whole-cell assays: expanding the scope of GPCR screening. Drug Discov Today 15(17–18):704–716

    CAS  PubMed  Google Scholar 

  267. Xi B, Yu N, Wang X, Xu X, Abassi YA (2008) The application of cell-based label-free technology in drug discovery. Biotechnol J 3(4):484–495

    CAS  PubMed  Google Scholar 

  268. Verdonk E, Johnson K, McGuinness R, Leung G, Chen YW, Tang HR, Michelotti JM, Liu VF (2006) Cellular dielectric spectroscopy: a label-free comprehensive platform for functional evaluation of endogenous receptors. Assay Drug Dev Technol 4(5):609–619

    CAS  PubMed  Google Scholar 

  269. Peters MF, Knappenberger KS, Wilkins D, Sygowski LA, Lazor LA, Liu J, Scott CW (2007) Evaluation of cellular dielectric spectroscopy, a whole-cell, label-free technology for drug discovery on Gi-coupled GPCRs. J Biomol Screen 12(3):312–319

    CAS  PubMed  Google Scholar 

  270. Flynn AN, Hoffman J, Tillu DV, Sherwood CL, Zhang Z, Patek R, Asiedu MN, Vagner J, Price TJ, Boitano S (2013) Development of highly potent protease-activated receptor 2 agonists via synthetic lipid tethering. FASEB J 27(4):1498–1510

    CAS  PubMed  PubMed Central  Google Scholar 

  271. Yu N, Atienza JM, Bernard J, Blanc S, Zhu J, Wang X, Xu X, Abassi YA (2006) Real-time monitoring of morphological changes in living cells by electronic cell sensor arrays: an approach to study G protein-coupled receptors. Anal Chem 78(1):35–43

    CAS  PubMed  Google Scholar 

  272. Zweemer AJ, Nederpelt I, Vrieling H, Hafith S, Doornbos ML, de Vries H, Abt J, Gross R, Stamos D, Saunders J, Smit MJ, Ijzerman AP, Heitman LH (2013) Multiple binding sites for small-molecule antagonists at the CC chemokine receptor 2. Mol Pharmacol 84(4):551–561

    CAS  PubMed  Google Scholar 

  273. Ciambrone GJ, Liu VF, Lin DC, McGuinness RP, Leung GK, Pitchford S (2004) Cellular dielectric spectroscopy: a powerful new approach to label-free cellular analysis. J Biomol Screen 9(6):467–480

    CAS  PubMed  Google Scholar 

  274. Chen AN, Malone DT, Pabreja K, Sexton PM, Christopoulos A, Canals M (2015) Detection and quantification of allosteric modulation of endogenous m4 muscarinic acetylcholine receptor using impedance-based label-free technology in a neuronal cell line. J Biomol Screen 20(5):646–654

    CAS  PubMed  Google Scholar 

  275. Lv S, Wu L, Cheng P, Yu J, Zhang A, Zha J, Liu J, Wang L, Di W, Hu M, Qi H, Li Y, Ding G (2010) Correlation of obesity and osteoporosis: effect of free fatty acids on bone marrow-derived mesenchymal stem cell differentiation. Exp Ther Med 1(4):603–610

    CAS  PubMed  PubMed Central  Google Scholar 

  276. Park HE, Kim D, Koh HS, Cho S, Sung JS, Kim JY (2011) Real-time monitoring of neural differentiation of human mesenchymal stem cells by electric cell-substrate impedance sensing. J Biomed Biotechnol 2011:485173

    PubMed  PubMed Central  Google Scholar 

  277. Tai YY, Chen RS, Lin Y, Ling TY, Chen MH (2012) FGF-9 accelerates epithelial invagination for ectodermal organogenesis in real time bioengineered organ manipulation. Cell Commun Signal 10(1):34

    CAS  PubMed  PubMed Central  Google Scholar 

  278. Cohen EN, Gao H, Anfossi S, Mego M, Reddy NG, Debeb B, Giordano A, Tin S, Wu Q, Garza RJ, Cristofanilli M, Mani SA, Croix DA, Ueno NT, Woodward WA, Luthra R, Krishnamurthy S, Reuben JM (2015) Inflammation mediated metastasis: immune induced epithelial-to-mesenchymal transition in inflammatory breast cancer cells. PLoS One 10(7):e0132710

    PubMed  PubMed Central  Google Scholar 

  279. Stolwijk JA, Hartmann C, Balani P, Albermann S, Keese CR, Giaever I, Wegener J (2011) Impedance analysis of adherent cells after in situ electroporation: non-invasive monitoring during intracellular manipulations. Biosens Bioelectron 26(12):4720–4727

    CAS  PubMed  Google Scholar 

  280. Chang YC, Stins MF, McCaffery MJ, Miller GF, Pare DR, Dam T, Paul-Satyasee M, Kim KS, Kwon-Chung KJ (2004) Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier. Infect Immun 72(9):4985–4995

    CAS  PubMed  PubMed Central  Google Scholar 

  281. Ebrahimi CM, Sheen TR, Renken CW, Gottlieb RA, Doran KS (2011) Contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitis. Infect Immun 79(7):2510–2518

    CAS  PubMed  PubMed Central  Google Scholar 

  282. Grab D, Nyarko E, Nikolskaia O, Kim Y, Dumler J (2009) Human brain microvascular endothelial cell traversal by Borrelia burgdorferi requires calcium signaling. Clin Microbiol Infect 15(5):422–426

    CAS  PubMed  Google Scholar 

  283. Lembo A, Gurney MA, Burnside K, Banerjee A, De Los Reyes M, Connelly JE, Lin WJ, Jewell KA, Vo A, Renken CW (2010) Regulation of CovR expression in Group B streptococcus impacts blood–brain barrier penetration. Mol Microbiol 77(2):431–443

    CAS  PubMed  PubMed Central  Google Scholar 

  284. Treeratanapiboon L, Psathaki K, Wegener J, Looareesuwan S, Galla H-J, Udomsangpetch R (2005) In vitro study of malaria parasite induced disruption of blood–brain barrier. Biochem Biophys Res Commun 335(3):810–818

    CAS  PubMed  Google Scholar 

  285. Goc A, Al-Azayzih A, Abdalla M, Al-Husein B, Kavuri S, Lee J, Moses K, Somanath PR (2013) P21 activated kinase-1 (Pak1) promotes prostate tumor growth and microinvasion via inhibition of transforming growth factor β expression and enhanced matrix metalloproteinase 9 secretion. J Biol Chem 288(5):3025–3035

    CAS  PubMed  Google Scholar 

  286. Goc A, Al-Husein B, Katsanevas K, Steinbach A, Lou U, Sabbineni H, DeRemer DL, Somanath PR (2014) Targeting Src-mediated Tyr216 phosphorylation and activation of GSK-3 in prostate cancer cells inhibit prostate cancer progression in vitro and in vivo. Oncotarget 5(3):775–787

    PubMed  PubMed Central  Google Scholar 

  287. Jiang WG, Ablin RJ, Kynaston HG, Mason MD (2009) The prostate transglutaminase (TGase-4, TGaseP) regulates the interaction of prostate cancer and vascular endothelial cells, a potential role for the ROCK pathway. Microvasc Res 77(2):150–157

    CAS  PubMed  Google Scholar 

  288. Keese CR, Bhawe K, Wegener J, Giaever I (2002) Real-time impedance assay to follow the invasive activities of metastatic cells in culture. Biotechniques 33(4):842–844, 846, 848-850

    CAS  PubMed  Google Scholar 

  289. Melnikova VO, Balasubramanian K, Villares GJ, Dobroff AS, Zigler M, Wang H, Petersson F, Price JE, Schroit A, Prieto VG (2009) Crosstalk between protease-activated receptor 1 and platelet-activating factor receptor regulates melanoma cell adhesion molecule (MCAM/MUC18) expression and melanoma metastasis. J Biol Chem 284(42):28845–28855

    CAS  PubMed  PubMed Central  Google Scholar 

  290. Ren J, Xiao Y-j, Singh LS, Zhao X, Zhao Z, Feng L, Rose TM, Prestwich GD, Xu Y (2006) Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells. Cancer Res 66(6):3006–3014

    CAS  PubMed  Google Scholar 

  291. Saxena NK, Sharma D, Ding X, Lin S, Marra F, Merlin D, Anania FA (2007) Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Res 67(6):2497–2507

    CAS  PubMed  PubMed Central  Google Scholar 

  292. Wang H-S, Hung Y, Su C-H, Peng S-T, Guo Y-J, Lai M-C, Liu C-Y, Hsu J-W (2005) CD44 cross-linking induces integrin-mediated adhesion and transendothelial migration in breast cancer cell line by up-regulation of LFA-1 (αLβ2) and VLA-4 (α4β1). Exp Cell Res 304(1):116–126

    CAS  PubMed  Google Scholar 

  293. Chen Y-W, Chen J-K, Wang J-S (2009) Exercise affects platelet-promoted tumor cell adhesion and invasion to endothelium. Eur J Appl Physiol 105(3):393–401

    PubMed  Google Scholar 

  294. Tsikitis VL, Morin NA, Harrington EO, Albina JE, Reichner JS (2004) The lectin-like domain of complement receptor 3 protects endothelial barrier function from activated neutrophils. J Immunol 173(2):1284–1291

    CAS  PubMed  Google Scholar 

  295. van Rijssel J, Kroon J, Hoogenboezem M, van Alphen FP, de Jong RJ, Kostadinova E, Geerts D, Hordijk PL, van Buul JD (2012) The Rho-guanine nucleotide exchange factor Trio controls leukocyte transendothelial migration by promoting docking structure formation. Mol Biol Cell 23(15):2831–2844

    PubMed  PubMed Central  Google Scholar 

  296. Zhu J, Wang X, Xu X, Abassi YA (2006) Dynamic and label-free monitoring of natural killer cell cytotoxic activity using electronic cell sensor arrays. J Immunol Methods 309(1):25–33

    CAS  PubMed  Google Scholar 

  297. Sansing HA, Renner NA, MacLean AG (2012) An inverted blood–brain barrier model that permits interactions between glia and inflammatory stimuli. J Neurosci Methods 207(1):91–96

    CAS  PubMed  PubMed Central  Google Scholar 

  298. Rother J, Richter C, Turco L, Knoch F, Mey I, Luther S, Janshoff A, Bodenschatz E, Tarantola M (2015) Crosstalk of cardiomyocytes and fibroblasts in co-cultures. Open Biol 5(6):150038

    CAS  PubMed  PubMed Central  Google Scholar 

  299. Yamamoto Y, Goda N, Nakamura T, Kusuhara T, Maruyama T, Mohri S, Kataoka N, Kajiya F (2007) Quantitative evaluation of effect for radiation exposure to cultured cells using electrical cell-substrate impedance sensing (ECIS) method. World Congress on medical physics and biomedical engineering 2006. Springer, Heidelberg, pp 1914–1917

    Google Scholar 

  300. Szulcek R, van Bezu J, Boonstra J, van Loon JJ, van Nieuw Amerongen GP (2015) Transient intervals of hyper-gravity enhance endothelial barrier integrity: impact of mechanical and gravitational forces measured electrically. PLoS One 10(12):e0144269

    PubMed  PubMed Central  Google Scholar 

  301. DePaola N, Phelps JE, Florez L, Keese CR, Minnear FL, Giaever I, Vincent P (2001) Electrical impedance of cultured endothelium under fluid flow. Ann Biomed Eng 29(8):648–656

    CAS  PubMed  Google Scholar 

  302. Phelps JE, DePaola N (2000) Spatial variations in endothelial barrier function in disturbed flows in vitro. Am J Physiol Heart Circ Physiol 278(2):H469–H476

    CAS  PubMed  Google Scholar 

  303. Seebach J, Dieterich P, Luo F, Schillers H, Vestweber D, Oberleithner H, Galla H-J, Schnittler H-J (2000) Endothelial barrier function under laminar fluid shear stress. Lab Invest 80(12):1819–1831

    CAS  PubMed  Google Scholar 

  304. Jaalouk DE, Lammerding J (2009) Mechanotransduction gone awry. Nat Rev Mol Cell Biol 10(1):63–73

    CAS  PubMed  PubMed Central  Google Scholar 

  305. Tarbell JM, Simon SI, Curry F-RE (2014) Mechanosensing at the vascular interface. Annu Rev Biomed Eng 16:505

    CAS  PubMed  PubMed Central  Google Scholar 

  306. Seebach J, Donnert G, Kronstein R, Werth S, Wojciak-Stothard B, Falzarano D, Mrowietz C, Hell SW, Schnittler H-J (2007) Regulation of endothelial barrier function during flow-induced conversion to an arterial phenotype. Cardiovasc Res 75(3):598–607

    Google Scholar 

  307. Clark PR, Jensen TJ, Kluger MS, Morelock M, Hanidu A, Qi Z, Tatake RJ, Pober JS (2011) MEK5 is activated by shear stress, activates ERK5 and induces KLF4 to modulate TNF responses in human dermal microvascular endothelial cells. Microcirculation 18(2):102–117

    CAS  PubMed  PubMed Central  Google Scholar 

  308. Shikata Y, Rios A, Kawkitinarong K, DePaola N, Garcia JG, Birukov KG (2005) Differential effects of shear stress and cyclic stretch on focal adhesion remodeling, site-specific FAK phosphorylation, and small GTPases in human lung endothelial cells. Exp Cell Res 304(1):40–49

    CAS  PubMed  Google Scholar 

  309. Bevan HS, Slater SC, Clarke H, Cahill PA, Mathieson PW, Welsh GI, Satchell SC (2011) Acute laminar shear stress reversibly increases human glomerular endothelial cell permeability via activation of endothelial nitric oxide synthase. Am J Physiol Renal Physiol 301(4):F733–F742

    PubMed  PubMed Central  Google Scholar 

  310. Siddharthan V, Kim YV, Liu S, Kim KS (2007) Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells. Brain Res 1147:39–50

    CAS  PubMed  PubMed Central  Google Scholar 

  311. Sircar M, Bradfield PF, Aurrand-Lions M, Fish RJ, Alcaide P, Yang L, Newton G, Lamont D, Sehrawat S, Mayadas T (2007) Neutrophil transmigration under shear flow conditions in vitro is junctional adhesion molecule-C independent. J Immunol 178(9):5879–5887

    CAS  PubMed  Google Scholar 

  312. Slater SC, Ramnath RD, Uttridge K, Saleem MA, Cahill PA, Mathieson PW, Welsh GI, Satchell SC (2012) Chronic exposure to laminar shear stress induces Kruppel-like factor 2 in glomerular endothelial cells and modulates interactions with co-cultured podocytes. Int J Biochem Cell Biol 44(9):1482–1490

    CAS  PubMed  Google Scholar 

  313. Ueno N, Harker KS, Clarke EV, McWhorter FY, Liu WF, Tenner AJ, Lodoen MB (2014) Real-time imaging of Toxoplasma-infected human monocytes under fluidic shear stress reveals rapid translocation of intracellular parasites across endothelial barriers. Cell Microbiol 16(4):580–595

    CAS  PubMed  Google Scholar 

  314. Matuszak J, Zaloga J, Friedrich RP, Lyer S, Nowak J, Odenbach S, Alexiou C, Cicha I (2015) Endothelial biocompatibility and accumulation of SPION under flow conditions. J Magn Magn Mater 380:20–26

    CAS  Google Scholar 

  315. Curtis TM, Widder MW, Brennan LM, Schwager SJ, van der Schalie WH, Fey J, Salazar N (2009) A portable cell-based impedance sensor for toxicity testing of drinking water. Lab Chip 9(15):2176–2183

    CAS  PubMed  Google Scholar 

  316. Zhang X, Li F, Nordin AN, Tarbell J, Voiculescu I (2015) Toxicity studies using mammalian cells and impedance spectroscopy method. Sens Biosens Res 3:112–121

    Google Scholar 

  317. Zhivotovsky B, Orrenius S (2010) Cell death mechanisms: cross-talk and role in disease. Exp Cell Res 316(8):1374–1383

    CAS  PubMed  Google Scholar 

  318. Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9(3):231–241

    CAS  PubMed  Google Scholar 

  319. Degterev A, Yuan J (2008) Expansion and evolution of cell death programmes. Nat Rev Mol Cell Biol 9(5):378–390

    CAS  PubMed  Google Scholar 

  320. Martin SJ, Henry CM (2013) Distinguishing between apoptosis, necrosis, necroptosis and other cell death modalities. Methods 61(2):87–89

    CAS  PubMed  Google Scholar 

  321. Tsujimoto Y (2012) Multiple ways to die: non-apoptotic forms of cell death. Acta Oncol 51(3):293–300

    CAS  PubMed  Google Scholar 

  322. Krysko DV, Berghe TV, Parthoens E, D’Herde K, Vandenabeele P (2008) Methods for distinguishing apoptotic from necrotic cells and measuring their clearance. Methods Enzymol 442:307–341

    PubMed  Google Scholar 

  323. Fauci AS (2008) Harrison’s principles of internal medicine, vol 2. McGraw-Hill, London

    Google Scholar 

  324. Tice RR, Austin CP, Kavlock RJ, Bucher JR (2013) Improving the human hazard characterization of chemicals: a Tox21 update. Environ Health Perspect 121(7):756

    PubMed  PubMed Central  Google Scholar 

  325. Nel A, Xia T, Meng H, Wang X, Lin S, Ji Z, Zhang H (2012) Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening. Acc Chem Res 46(3):607–621

    PubMed  PubMed Central  Google Scholar 

  326. Niles AL, Moravec RA, Riss TL (2009) In vitro viability and cytotoxicity testing and same-well multi-parametric combinations for high throughput screening. Curr Chem Genom 3:33–41

    CAS  Google Scholar 

  327. Giaever I, Keese C (1992) Toxic? Cells can tell. ChemTech 22(2):116–125

    CAS  Google Scholar 

  328. Keese C, Karra N, Dillon B, Goldberg A, Giaever I (1998) Cell-substratum interactions as a predictor of cytotoxicity. In Vitro Mol Toxicol 11(2):183–192

    CAS  Google Scholar 

  329. Curtis TM, Tabb J, Romeo L, Schwager SJ, Widder MW, van der Schalie WH (2009) Improved cell sensitivity and longevity in a rapid impedance-based toxicity sensor. J Appl Toxicol 29(5):374–380

    CAS  PubMed  Google Scholar 

  330. Kubisch R, Bohrn U, Fleischer M, Stutz E (2012) Cell-based sensor system using L6 cells for broad band continuous pollutant monitoring in aquatic environments. Sensors 12(3):3370–3393

    CAS  PubMed  PubMed Central  Google Scholar 

  331. Lee WK, Torchalski B, Kohistani N, Thevenod F (2011) ABCB1 protects kidney proximal tubule cells against cadmium-induced apoptosis: roles of cadmium and ceramide transport. Toxicol Sci 121(2):343–356

    CAS  PubMed  Google Scholar 

  332. Xing JZ, Zhu L, Jackson JA, Gabos S, Sun XJ, Wang XB, Xu X (2005) Dynamic monitoring of cytotoxicity on microelectronic sensors. Chem Res Toxicol 18(2):154–161

    CAS  PubMed  Google Scholar 

  333. Atienzar FA, Tilmant K, Gerets HH, Toussaint G, Speeckaert S, Hanon E, Depelchin O, Dhalluin S (2011) The use of real-time cell analyzer technology in drug discovery: defining optimal cell culture conditions and assay reproducibility with different adherent cellular models. J Biomol Screen 16(6):575–587

    CAS  PubMed  Google Scholar 

  334. Pauly D, Worbs S, Kirchner S, Shatohina O, Dorner MB, Dorner BG (2012) Real-time cytotoxicity assay for rapid and sensitive detection of ricin from complex matrices. PLoS One 7(4):e35360

    CAS  PubMed  PubMed Central  Google Scholar 

  335. Alborzinia H, Can S, Holenya P, Scholl C, Lederer E, Kitanovic I, Wolfl S (2011) Real-time monitoring of cisplatin-induced cell death. PLoS One 6(5):e19714

    CAS  PubMed  PubMed Central  Google Scholar 

  336. Otero-Gonzalez L, Sierra-Alvarez R, Boitano S, Field JA (2012) Application and validation of an impedance-based real time cell analyzer to measure the toxicity of nanoparticles impacting human bronchial epithelial cells. Environ Sci Technol 46(18):10271–10278

    CAS  PubMed  Google Scholar 

  337. Sergent JA, Paget V, Chevillard S (2012) Toxicity and genotoxicity of nano-SiO2 on human epithelial intestinal HT-29 cell line. Ann Occup Hyg 56(5):622–630

    CAS  PubMed  Google Scholar 

  338. Campbell CE, Laane MM, Haugarvoll E, Giaever I (2007) Monitoring viral-induced cell death using electric cell-substrate impedance sensing. Biosens Bioelectron 23(4):536–542

    CAS  PubMed  Google Scholar 

  339. McCoy MH, Wang E (2005) Use of electric cell-substrate impedance sensing as a tool for quantifying cytopathic effect in influenza A virus infected MDCK cells in real-time. J Virol Methods 130(1–2):157–161

    CAS  PubMed  Google Scholar 

  340. Muller J, Thirion C, Pfaffl MW (2011) Electric cell-substrate impedance sensing (ECIS) based real-time measurement of titer dependent cytotoxicity induced by adenoviral vectors in an IPI-2I cell culture model. Biosens Bioelectron 26(5):2000–2005

    PubMed  Google Scholar 

  341. Benachour H, Bastogne T, Toussaint M, Chemli Y, Seve A, Frochot C, Lux F, Tillement O, Vanderesse R, Barberi-Heyob M (2012) Real-time monitoring of photocytotoxicity in nanoparticles-based photodynamic therapy: a model-based approach. PLoS One 7(11):e48617

    CAS  PubMed  PubMed Central  Google Scholar 

  342. Arndt S, Seebach J, Psathaki K, Galla HJ, Wegener J (2004) Bioelectrical impedance assay to monitor changes in cell shape during apoptosis. Biosens Bioelectron 19(6):583–594

    CAS  PubMed  Google Scholar 

  343. Huang L, Xie L, Boyd JM, Li XF (2008) Cell-electronic sensing of particle-induced cellular responses. Analyst 133(5):643–648

    CAS  PubMed  Google Scholar 

  344. Qiu Y, Liao R, Zhang X (2009) Impedance-based monitoring of ongoing cardiomyocyte death induced by tumor necrosis factor-alpha. Biophys J 96(5):1985–1991

    CAS  PubMed  PubMed Central  Google Scholar 

  345. Xiao C, Luong JH (2005) Assessment of cytotoxicity by emerging impedance spectroscopy. Toxicol Appl Pharmacol 206(2):102–112

    CAS  PubMed  Google Scholar 

  346. Janshoff A, Wegener J, Sieber M, Galla HJ (1996) Double-mode impedance analysis of epithelial cell monolayers cultured on shear wave resonators. Eur Biophys J 25(2):93–103

    CAS  PubMed  Google Scholar 

  347. Liu F, Voiculescu I, Nordin AN, Li F (2013) Water toxicity detection using cell-based hybrid biosensors. Sensors. IEEE, Piscataway, pp 1–5

    Google Scholar 

  348. Steinem C, Janshoff A, Wegener J, Ulrich WP, Willenbrink W, Sieber M, Galla HJ (1997) Impedance and shear wave resonance analysis of ligand-receptor interactions at functionalized surfaces and of cell monolayers. Biosens Bioelectron 12(8):787–808

    CAS  PubMed  Google Scholar 

  349. Michaelis S, Wegener J, Robelek R (2013) Label-free monitoring of cell-based assays: combining impedance analysis with SPR for multiparametric cell profiling. Biosens Bioelectron 49:63–70

    CAS  PubMed  Google Scholar 

  350. Alexander FA, Price DT, Bhansali S (2013) From cellular cultures to cellular spheroids: is impedance spectroscopy a viable tool for monitoring multicellular spheroid (MCS) drug models? IEEE Rev Biomed Eng 6:63–76

    PubMed  Google Scholar 

  351. Kloß D, Kurz R, Jahnke H-G, Fischer M, Rothermel A, Anderegg U, Simon JC, Robitzki AA (2008) Microcavity array (MCA)-based biosensor chip for functional drug screening of 3D tissue models. Biosens Bioelectron 23(10):1473–1480

    PubMed  Google Scholar 

  352. Thielecke H, Mack A, Robitzki A (2001) A multicellular spheroid-based sensor for anti-cancer therapeutics. Biosens Bioelectron 16(4):261–269

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge financial support by the Research Training Group 1910 “Medicinal chemistry of selective GPCR ligands” funded by the German Research Foundation (DFG) (grant number 222125149) as well as support by a regular DFG research grant (grant number 253182429). JS is particularly grateful for a scholarship granted by the Bavarian Gender Equality Program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joachim Wegener .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Stolwijk, J.A., Wegener, J. (2019). Impedance-Based Assays Along the Life Span of Adherent Mammalian Cells In Vitro: From Initial Adhesion to Cell Death. In: Wegener, J. (eds) Label-Free Monitoring of Cells in vitro. Bioanalytical Reviews, vol 2. Springer, Cham. https://doi.org/10.1007/11663_2019_7

Download citation

Publish with us

Policies and ethics