Assessment of effects of multi drug resistance on dielectric properties of K562 leukemic cells using electrorotation

Bahrieh, Garsha
Erdem, Murat
Ozgur, Ebru
Gündüz, Ufuk
Külah, Haluk
In this study, dielectric characterization of multidrug resistant (MDR) K562 human leukemia cells was carried out using a MEMS based electrorotation (ER) device with 3D electrodes. P-glycoprotein (P-gp) dependent MDR causes variation in cell dielectric properties (cell interior conductivity (sigma(i)), membrane capacitance (C-m) and total effective membrane conductance (G(m)*)) due to overexpression of P-gp, which modulates the activity of membrane-bound Cl- channels. Different cell populations resistant to varying levels of doxorubicin (DOX, 0.1-0.5 mu M) and imatinib (IMA, 0.2-0.5 mu M) were studied to reveal the relationship between cell dielectric properties and the degree of drug resistance. ER characterization results proved considerable changes in cell membrane and interior dielectric properties as the resistance level to chemotherapeutic drugs changes. The membrane dielectric properties of the cells increase significantly at low (0.1-0.2 mu M) drug resistance levels (K562/IMA-0.2: C-m = 15.63 +/- 3.02 mF m(-2) and G(m)* = 2953 +/- 82 S m(-2), and K562/DOX-0.1: C-m = 12.29 +/- 2.15 mF m(-2) and G(m)* = 1810 +/- 14 S m(-2)), compared to the sensitive ones (C-m = 8.93 +/- 1.43 mF m(-2) and G(m)* = 336 +/- 73 S m(-2)). However, they follow a decreasing trend as the drug resistance level increases (0.3-0.5 mu M). The membrane capacitance and effective conductance for IMA resistant K562 cells falls to 8.10 +/- 1.69 mF m(-2) and 113 +/- 18 S m(-2) in 0.5 mu M resistant cells, respectively. Similarly, the membrane capacitance and effective conductance of DOX resistant cells falls to 8.70 +/- 1.71 mF m(-2) and 1377 +/- 22 S m(-2) in 0.5 mu M resistant cells, respectively. However, no direct relationship could be observed between increased drug resistance and cell interior conductivity, which showed an oscillating behavior. Results prove that the degree of drug resistance significantly affects the dielectric properties of K562 cells, although they possess a similar size and morphology. Variations in cell dielectric properties result in differences in DEP crossover frequencies, which could be utilized in the detection and separation of MDR using dielectrophoretic based devices.


Dielectric Analysis of Changes in Electric Properties of Doxorubicin Resistant K562 Leukemic Cells Through Electrorotation with 3 D Electrodes
Garsha, Bahrieh; Erdem, Murat; Özgür, Ebru; Gündüz, Ufuk; Külah, Haluk (2013-10-31)
In this study, dielectric characterization of multidrug resistant (MDR) K562 human leukemia cells was carried out using a MEMS-based electrorotation (ER) device with 3D electrodes. Different cell populations were utilized, which were resistant to 0.1, 0.3, and 0.5 μM doxorubicin. The ER devices with 3D quadruple electrodes (30 urn in height) were used, in order to eliminate the fringing field effect on the rotation of cells. Signals in phase quadrature were applied to the polynomial electrodes, to induce th...
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This study presents label-free detection of imatinib resistance in K562 cells via integrated dielectrophoretic detection and impedimetric counting on a lab-on-a-chip system. Two impedimetric counting units were placed upstream and downstream of dielectrophoretic detection unit to obtain differential cell count and consequently the trapping ratio. The trapping ratio up to 57% was achieved for imatinib resistant (~60-fold) K562 cells, while it was minimized to 20% for wild type K562 cells
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Drug resistance, a major obstacle in chemotherapy, is the sum of several cellular alterations including resistance to induction of apoptosis. Apoptosis is a well-regulated cell death mechanism which is controlled by several signaling pathways and a vast number of proteins. Alterations in the proteins involved in the apoptotic regulation have been associated with drug resistance in cancer. Programmed Cell Death 10 (PDCD10) protein is a novel apoptotic regulator that is recently linked to the modulation of ce...
Citation Formats
G. Bahrieh, M. Erdem, E. Ozgur, U. Gündüz, and H. Külah, “Assessment of effects of multi drug resistance on dielectric properties of K562 leukemic cells using electrorotation,” RSC ADVANCES, pp. 44879–44887, 2014, Accessed: 00, 2020. [Online]. Available: