Characterization of sequentially-staged cancer cells using electrorotation

English version

Autoři: Claudia I. Trainito ^aff001; Daniel C. Sweeney ^aff002; Jaka Čemažar ^aff002; Eva M. Schmelz ^aff003; Olivier Français ^aff001; Bruno Le Pioufle ^aff001; Rafael V. Davalos ^aff002
Působiště autorů: CNRS SATIE Institut d’Alembert ENS Paris Saclay, France ^aff001; Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia, United States of America ^aff002; Department of Human Nutrition, Food, and Exercise, Virginia Tech, Blacksburg, Virginia, United States of America ^aff003; ESIEE-Paris, ESYCOM (FRE 2028), UPE, Noisy-Le-Grand, France ^aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0222289

Souhrn

The identification and separation of cells from heterogeneous populations is critical to the diagnosis of diseases. Label-free methodologies in particular have been developed to manipulate individual cells using properties such as density and morphology. The electrical properties of malignant cells, including the membrane capacitance and cytoplasmic conductivity, have been demonstrated to be altered compared to non-malignant cells of similar origin. Here, we exploit these changes to characterize individual cells in a sequentially-staged in vitro cancer model using electrorotation (EROT)—the rotation of a cell induced by a rotating electric field. Using a microfabricated device, a dielectrophoretic force to suspend cells while measuring their angular velocity resulting from an EROT force applied at frequencies between 3 kHz to 10 MHz. We experimentally determine the EROT response for cells at three stages of malignancy and analyze the resultant spectra by considering models that include the effect of the cell membrane alone (single-shell model) and the combined effect of the cell membrane and nucleus (double-shell model). We find that the cell membrane is largely responsible for a given cell’s EROT response between 3 kHz and 10 MHz. Our results also indicate that membrane capacitance, membrane conductance, and cytoplasmic conductivity increase with an increasingly malignant phenotype. Our results demonstrate the potential of using electrorotation as a means making of non-invasive measurements to characterize the dielectric properties of cancer cells.

Klíčová slova:

Biology and life sciences – Cell biology – Physical sciences – Research and analysis methods – Medicine and health sciences – Cellular structures and organelles – Materials science – Materials – Cytoplasm – Diagnostic medicine – Oncology – Cell membranes – Physics – Cancer detection and diagnosis – Bioassays and physiological analysis – Electrophysiological techniques – Material properties – Electricity – Electric field – Electric conductivity – Capacitance – Insulators – Dielectrics – Membrane electrophysiology

Zdroje

1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70. doi: 10.1016/S0092-8674(00)81683-9

2. Chatterjee SK, Zetter BR. Cancer biomarkers: knowing the present and predicting the future. Future Onncology. 2005;1(1):37–50. doi: 10.1517/14796694.1.1.37

3. Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, et al. Serum protein markers for early detection of ovarian cancer. Proceedings of the National Academy of Sciences. 2005;102(21):7677–7682. doi: 10.1073/pnas.0502178102

4. Fredriksson S, Dixon W, Ji H, Koong AC, Mindrinos M, Davis RW. Multiplexed protein detection by proximity ligation for cancer biomarker validation. Nature methods. 2007;4(4):327. doi: 10.1038/nmeth1020

5. Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schütze K, et al. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. The American Journal of Pathology. 2000;156(1):57–63. doi: 10.1016/S0002-9440(10)64706-2

6. Mohamed H, Murray M, Turner JN, Caggana M. Isolation of tumor cells using size and deformation. Journal of Chromatography A. 2009;1216(47):8289–8295. doi: 10.1016/j.chroma.2009.05.036

7. Wang K, Zhao Y, Chen D, Huang C, Fan B, Long R, et al. The instrumentation of a microfluidic analyzer enabling the characterization of the specific membrane capacitance, cytoplasm conductivity, and instantaneous young’s modulus of single cells. International Journal of Molecular Sciences. 2017;18(6):1–8. doi: 10.3390/ijms18061158

8. Gascoyne PR, Noshari J, Anderson TJ, Becker FF. Isolation of rare cells from cell mixtures by dielectrophoresis. Electrophoresis. 2009;30(8):1388–1398. doi: 10.1002/elps.200800373

9. Douglas TA, Cemazar J, Balani N, Sweeney DC, Schmelz EM, Davalos RV. A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow. Electrophoresis. 2017;38(11):1507–1514. doi: 10.1002/elps.201770085

10. Čemažar J, Douglas TA, Schmelz EM, Davalos RV. Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures. Biomicrofluidics. 2016;10(1):014109. doi: 10.1063/1.4939947

11. Salmanzadeh A, Romero L, Shafiee H, Gallo-Villanueva RC, Stremler Ma, Cramer SD, et al. Isolation of prostate tumor initiating cells (TICs) through their dielectrophoretic signature. Lab on a chip. 2012;12(1):182–9. doi: 10.1039/C1LC20701F

12. Creekmore AL, Silkworth WT, Cimini D, Jensen RV, Roberts PC, Schmelz EM. Changes in gene expression and cellular architecture in an ovarian cancer progression model. PloS one. 2011;6(3):e17676. doi: 10.1371/journal.pone.0017676

13. Becker F, Wang XB, Huang Y, Pethig R, Vykoukal J, Gascoyne P. The removal of human leukaemia cells from blood using interdigitated microelectrodes. Journal of Physics D: Applied Physics. 1994;27(12):2659. doi: 10.1088/0022-3727/27/12/030

14. Becker FF, Wang XB, Huang Y, Pethig R, Vykoukal J, Gascoyne P. Separation of human breast cancer cells from blood by differential dielectric affinity. Proceedings of the National Academy of Sciences. 1995;92(3):860–864. doi: 10.1073/pnas.92.3.860

15. Surowiec AJ, Stuchly SS, Barr JR, Swarup A. Dielectric properties of breast carcinoma and the surrounding tissues. IEEE Transactions on Biomedical Engineering. 1988;35(4):257–263. doi: 10.1109/10.1374

16. Gascoyne P, Mahidol C, Ruchirawat M, Satayavivad J, Watcherasit P, F B. microsample preparation by dielectrophoresis: isolation of malaria. Lab On A Chip. 2002;2(2):70–75. doi: 10.1039/b110990c

17. Salomon S, Leichlé T, Nicu L. A dielectrophoretic continuous flow sorter using integrated microelectrodes coupled to a channel constriction. Electrophoresis. 2011;32(12):1508–1514. doi: 10.1002/elps.201000675

18. Pohl H. Some effects of nonuniform fields on dielectrics. Journal of Applied Physics. 1958;29(8):1182–1188. doi: 10.1063/1.1723398

19. Pethig R, Talary MS, Lee RS. Enhancing traveling-wave dielectrophoresis with signal superposition. IEEE Engineering in Medicine and Biology. 2003;22(6):43–50. doi: 10.1109/MEMB.2003.1266046

20. Morgan H, Green NG. AC electrokinetics. Research Studies Press,; 2003.

21. Salmanzadeh A, Kittur H, Sano MB, Roberts PC, Schmelz EM, Davalos RV. Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis. Biomicrofluidics. 2012;6(2):24104–2410413. doi: 10.1063/1.3699973

22. Sano MB, Caldwell JL, Davalos RV. Modeling and development of a low frequency contactless dielectrophoresis (cDEP) platform to sort cancer cells from dilute whole blood samples. Biosensors and Bioelectronics. 2011;30(1):13–20. doi: 10.1016/j.bios.2011.07.048

23. Arnold W M Z U. Electro-rotation: development of a technique for dielectric measurements on individual cells and particles. Journal of Electrostatics. 1998;21(2-3):151–191. doi: 10.1016/0304-3886(88)90027-7

24. Pethig R, Jakubek LM, Sanger RH, Heart E, Corson ED, Smith PJ. Electrokinetic measurements of membrane capacitance and conductance for pancreatic beta-cells. IEEE Proceedings–Nanobiotechnology. 2005;152(6):189–193.

25. Han SI H KH Joo YD. An electrorotation technique for measuring the dielectric properties of cells with simultaneous use of negative quadrupolar dielectrophoresis and electrorotation. IEEE Proceedings–Nanobiotechnology. 2013;138(5):1529–1537.

26. Yang J, Huang Y, Wang X, Wang XB, Becker FF, Gascoyne PR. Dielectric properties of human leukocyte subpopulations determined by electrorotation as a cell separation criterion. Biophysical Journal. 1999;76(6):3307–3314. doi: 10.1016/S0006-3495(99)77483-7

27. Salmanzadeh A, Sano MB, Gallo-Villanueva RC, Roberts PC, Schmelz EM, Davalos RV. Investigating dielectric properties of different stages of syngeneic murine ovarian cancer cells. Biomicrofluidics. 2013;7(1):11809. doi: 10.1063/1.4788921

28. Salmanzadeh A, Elvington ES, Roberts PC, Schmelz EM, Davalos RV. Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model. Integrative biology: quantitative biosciences from nano to macro. 2013;5(6):843–52. doi: 10.1039/c3ib00008g

29. Jiang WG. Focus on science—membrane ruffling of cancer cells: a parameter of tumour cell motility and invasion. European Journal of Surgical Oncology (EJSO). 1995;21(3):307–309. doi: 10.1016/S0748-7983(95)91690-3

30. Huang Y, Pethig R. Electrode design for negative dielectrophoresis. Measurement Science and Technology. 1991;2(12):1142. doi: 10.1088/0957-0233/2/12/005

31. Pethig R, Huang Y, Wang Xb, Burt JP. Positive and negative dielectrophoretic collection of colloidal particles using interdigitated castellated microelectrodes. Journal of Physics D: Applied Physics. 1992;25(5):881. doi: 10.1088/0022-3727/25/5/022

32. Huang Y, Holzel R, Pethig R, Wang XB. Differences in the AC electrodynamics of viable and non-viable yeast cells determined through combined dielectrophoresis and electrorotation studies. Physics in Medicine and Biology. 1992;37(7):1499–1517. doi: 10.1088/0031-9155/37/7/003

33. Arnold W, Zimmermann U. Electro-rotation: development of a technique for dielectric measurements on individual cells and particles. Journal of Electrostatics. 1988;21(2-3):151–191. doi: 10.1016/0304-3886(88)90027-7

34. Gascoyne PRC, Huang Y, Pethig R, Vykoukal J, Becker FF. Dielectrophoretic separation of mammalian cells studied by computerized image analysis. Measurement Science and Technology. 1992;3(5):439–445. doi: 10.1088/0957-0233/3/5/001

35. Roberts PC, Mottillo EP, Baxa AC, Heng HH, Doyon-Reale N, Gregoire L, et al. Sequential molecular and cellular events during neoplastic progression: a mouse syngeneic ovarian cancer model. Neoplasia. 2005;7(10):944–956. doi: 10.1593/neo.05358

36. Cohen CA, Shea AA, Heffron CL, Schmelz EM, Roberts PC. The parity-associated microenvironmental niche in the omental fat band is refractory to ovarian cancer metastasis. Cancer Prevention Research. 2013;6(11):1182–1193. doi: 10.1158/1940-6207.CAPR-13-0227

37. Anderson AS, Roberts PC, Frisard MI, McMillan RP, Brown TJ, Lawless MH, et al. Metabolic changes during ovarian cancer progression as targets for sphingosine treatment. Experimental Cell Research. 2013;319(10):1431–1442. doi: 10.1016/j.yexcr.2013.02.017

38. Trainito CI, Français O, Le Pioufle B. Monitoring the permeabilization of a single cell in a microfluidic device, through the estimation of its dielectric properties based on combined dielectrophoresis and electrorotation in situ experiments. Electrophoresis. 2015;36(9-10):1115–1122. doi: 10.1002/elps.201400482

39. Foreman-Mackey D, Hogg DW, Lang D, Goodman J. emcee: the MCMC hammer. Publications of the Astronomical Society of the Pacific. 2013;125(925):306. doi: 10.1086/670067

40. Kirby RC, Logg A. A Compiler for Variational Forms. ACM Transactions on Mathematical Software (TOMS). 2006;32(3):417–444. doi: 10.1145/1163641.1163644

41. Geuzaine C. Gmsh: a three-dimensional finite element mesh generator with built-in pre- and post-processing facilities. International Journal for Numerical Methods in Engineering. 2009;79(11):1309–1331. doi: 10.1002/nme.2579

42. Buchner R, Barthel J, Stauber J. The dielectric relaxation of water between 0°C and 35°C. Chemical Physics Letters. 1999;306(1-2):57–63. doi: 10.1016/S0009-2614(99)00455-8

43. Kestin J, Sokolov M, Wakeham WA. Viscosity of liquid water in the range 8°C to 150°C. Journal of Physical and Chemical Reference Data. 1978;7(3):941–948. doi: 10.1063/1.555581

44. Marszalek P, Zielinsky JJ, Fikus M, Tsong TY. Determination of electric parameters of cell membranes by a dielectrophoresis method. Biophysical journal. 1991;59(5):982–7. doi: 10.1016/S0006-3495(91)82312-8

45. Hu Q, Joshi RP, Beskok A. Model study of electroporation effects on the dielectrophoretic response of spheroidal cells. Journal of Applied Physics. 2009;106(2):1–8. doi: 10.1063/1.3173344

46. Gascoyne PR, Pethig R, Burt JP, Becker FF. Membrane changes accompanying the induced differentiation of Friend murine erythroleukemia cells studied by dielectrophoresis. Biochimica et Biophysica Acta (BBA)-Biomembranes. 1993;1149(1):119–126. doi: 10.1016/0005-2736(93)90032-U

47. Hölzel R, Lamprecht I. Dielectric properties of yeast cells as determined by electrorotation. Biochimica et Biophysica Acta (BBA)—Biomembranes. 1992;1104(1):195–200. doi: 10.1016/0005-2736(92)90150-K

48. Alberts B. Molecular Biology of the Cell in Cell 4th; 2002.

49. Bhonsle SP, Arena CB, Sweeney DC, Davalos RV. Mitigation of impedance changes due to electroporation therapy using bursts of high-frequency bipolar pulses. BioMedical Engineering OnLine. 2015;14(S3):1–14.

50. Braschler T, Demierre N, Nascimento E, Silva T, Oliva AG, Renaud P. Continuous separation of cells by balanced dielectrophoretic forces at multiple frequencies. Lab on a chip. 2008;8(2):280–6. doi: 10.1039/B710303D

Characterization of sequentially-staged cancer cells using electrorotation

Souhrn

Klíčová slova:

Zdroje

PLOS One

Aktuální možnosti diagnostiky a léčby litiáz