The Measurement and Analysis of Impedance Response of HeLa Cells to Distinct Chemotherapy Drugs

Electric cell–substrate impedance sensing exhibits a real-time and label-free feature to monitor the response of cells stimulated by various biochemical and mechanical signals. Alterations in the currents passing through the cell–electrode system characterize the impedance variations of cells. The impedance responses of HeLa cells under distinct chemotherapy drugs combine the effects of cell proliferation and cell–substrate adhesion. Optimal interdigitated electrodes were selected to explore the impedance responses of HeLa cells. Measurements of impedance of cells in response to three widely used chemotherapy drugs in clinical practice, namely cisplatin, doxorubicin, 5-fluorouracil, were performed. The results demonstrated that distinct impedance responses of HeLa cells to drugs were exhibited and a decrease in measured impedance was observed after drug treatment, accompanied by alterations in the distribution and intensity of the adhesion-related protein vinculin and the rate of cell proliferation. The link between the impedance profiles of HeLa cells and their biological functions was developed based on the circuit model. This study demonstrated the weights of cell proliferation and adhesion of HeLa cells under the treatments of DDP, DOX, and 5-FU, resulted in distinct impedance responses of cells, providing an impedance-based evaluation methodology for cervical cancer treatment.

Download Full-text

Electric cell-substrate impedance sensing in kidney research

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz191 ◽

2019 ◽

Author(s):

Takamasa Iwakura ◽

Julian A Marschner ◽

Zhi Bo Zhao ◽

Monika Katarzyna Świderska ◽

Hans-Joachim Anders

Keyword(s):

Continuous Monitoring ◽

Adherent Cells ◽

Label Free ◽

Impedance Sensing ◽

Barrier Integrity ◽

Practical Applications ◽

Non Invasive ◽

Glomerular Epithelial Cells ◽

Cell Substrate ◽

Wide Range

Abstract Electric cell-substrate impedance sensing (ECIS) is a quantitative, label-free, non-invasive analytical method allowing continuous monitoring of the behaviour of adherent cells by online recording of transcellular impedance. ECIS offers a wide range of practical applications to study cell proliferation, migration, differentiation, toxicity and monolayer barrier integrity. All of these applications are relevant for basic kidney research, e.g. on endothelial cells, tubular and glomerular epithelial cells. This review gives an overview on the fundamental principles of the ECIS technology. We name strengths and remaining hurdles for practical applications, present an ECIS array reuse protocol, and review its past, present and potential future contributions to preclinical kidney research.

Download Full-text

Real-time label-free monitoring of adipose-derived stem cell differentiation with electric cell-substrate impedance sensing

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1018260108 ◽

2011 ◽

Vol 108 (16) ◽

pp. 6462-6467 ◽

Cited By ~ 144

Author(s):

P. O. Bagnaninchi ◽

N. Drummond

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Real Time ◽

Stem Cell Differentiation ◽

Label Free ◽

Impedance Sensing ◽

Cell Substrate ◽

Adipose Derived Stem Cell

Download Full-text

A Screening Approach for Identifying Gliadin Neutralizing Antibodies on Epithelial Intestinal Caco-2 Cells

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555217697435 ◽

2017 ◽

Vol 22 (8) ◽

pp. 1035-1043

Author(s):

Harald Hundsberger ◽

Anita Koppensteiner ◽

Elisabeth Hofmann ◽

Doris Ripper ◽

Maren Pflüger ◽

...

Keyword(s):

High Throughput Screening ◽

Neutralizing Antibodies ◽

Inflammatory Condition ◽

Gluten Free ◽

Label Free ◽

Industrialized Countries ◽

Therapeutic Approaches ◽

Impedance Sensing ◽

Cell Substrate ◽

Chronic Inflammatory Condition

Celiac disease (CD) is a chronic inflammatory condition caused by the ingestion of gliadin-containing food in genetically susceptible individuals. Undigested peptides of gliadin exert various effects, including increased intestinal permeability and inflammation in the small intestine. Although many therapeutic approaches are in development, a gluten-free diet is the only effective treatment for CD. Affecting at least 1% of the population in industrialized countries, it is important to generate therapeutic options against CD. Here, we describe the establishment of a high-throughput screening (HTS) platform based on AlphaLISA and electrical cell–substrate impedance sensing (ECIS) technology for the identification of anti-inflammatory and barrier-protective compounds in human enterocytes after pepsin-trypsin-digested gliadin (PT-gliadin) treatment. Our results show that the combination of these HTS technologies enables fast, reliable, simple, and label-free screening of IgY antibodies against PT-gliadin. Using this platform, we have identified a new chicken anti-PT-gliadin IgY antibody as a potential anti-CD agent.

Download Full-text

Stretchable impedance sensor for mammalian cell proliferation measurements

Lab on a Chip ◽

10.1039/c7lc00375g ◽

2017 ◽

Vol 17 (12) ◽

pp. 2054-2066 ◽

Cited By ~ 12

Author(s):

Xudong Zhang ◽

William Wang ◽

Fang Li ◽

Ioana Voiculescu

Keyword(s):

Cell Proliferation ◽

Mammalian Cell ◽

Lab On A Chip ◽

Impedance Sensing ◽

Cell Substrate ◽

Impedance Sensor

This paper presents the fabrication and testing of a novel stretchable electric cell–substrate impedance sensing (ECIS) lab on a chip device.

Download Full-text

Comparison of Leading Biosensor Technologies to Measure Endothelial Adhesion, Barrier Properties, and Responses to Cytokines in Real-Time

Proceedings ◽

10.3390/iecb2020-07036 ◽

2020 ◽

Vol 60 (1) ◽

pp. 62

Author(s):

James J. W. Hucklesby ◽

Akshata Anchan ◽

Simon J. O’Carroll ◽

Catherine E. Angel ◽

E. Scott Graham

Keyword(s):

Real Time ◽

Barrier Properties ◽

Microvascular Endothelial Cell ◽

Label Free ◽

Adhesion Barrier ◽

Impedance Sensing ◽

Non Invasive ◽

Reduced Frequency ◽

Cell Substrate ◽

Higher Sensitivity

Electric Cell-substrate Impedance Sensing (ECIS), xCELLigence and cellZscope are commercially available instruments which are able to measure the impedance of cellular monolayers continuously and with high precision. The small currents used allow the label-free, real-time monitoring of the cells in a non-invasive manner. Despite the widespread use of these systems individually, direct comparisons between the systems have not been published. In order to compare the sensitivity of the instruments, the responses of the brain microvascular endothelial cell line hCMVEC to the inflammatory cytokines TNFα and IL1β were measured on all three instruments simultaneously. All three instruments showed transient decreases, followed by prolonged increases in impedance. Although xCELLigence could detect these changes, it was unable to determine which component of the barrier was affected. In contrast, ECIS and cellZscope were both able to attribute responses to particular barrier components, and ECIS had a higher sensitivity than cellZscope. Finally, as cellZscope uses Transwells, it allows access to the basolateral compartment, an important advantage of this technology. Furthermore, although xCELLigence readings are equivalent to ECIS, the reduced frequency range greatly limits interpretation. This work demonstrates that instruments must be carefully selected in order to ensure that they are appropriate for the experimental questions being asked.

Download Full-text

miR-140-Modified Bone Marrow Mesenchymal Stem Cells Enhance Chemotherapy Sensitization in Cervical Squamous Cell Carcinoma Cells via Targeting Microtubule Depolymerization Protein 1 (STMN1)

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2883 ◽

2022 ◽

Vol 12 (1) ◽

pp. 232-238

Author(s):

Xiaoli Guo ◽

Xiaodong Cheng

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Mesenchymal Stem Cells ◽

Hela Cells ◽

Cervical Squamous Cell Carcinoma ◽

Survivin Mrna ◽

Chemotherapy Drugs ◽

Marrow Mesenchymal Stem Cells

Effect of bone marrow mesenchymal stem cells (BMSCs) on the sensitivity of chemotherapy drugs and microRNAs (miRNAs) is still unclear. This study explored the role of miR-140 modified BMSCs in enhancing paclitaxel sensitivity of cervical squamous cell carcinoma (CSCC). Hela cells, BMSCs cells, and miR-140 modified BMSCs were transfected with miR-140 mimic, miR-140 inhibitor, and miR-140 NC, respectively. After transfection, they were co-cultured with Hela cells and paclitaxel to set up miR-140 mimic group, miR-140 inhibitor group, and miR-140 NC group (without paclitaxel treatment) followed by analysis of cell proliferation, apoptosis, ROS generation, expression of miR-140, STMN1, STAT3, p-STAT3, and survivin mRNA and protein. miR-140 inhibitor group showed lowest cell proliferation number and expressions of miR-140, STMN1, STAT3, p-STAT3, and survivin mRNA and protein with highest number of apoptotic cells, which were all reversed in miR-140 mimic group. There was a positive correlation between STMN1 level and miR-140 expression (r = 0.449, P = 0.108). BMSCs modified with miR-140 inhibitor can target STMN1, enhance the sensitivity of chemotherapy drugs, and exert an inhibitory effect on CSCC cell proliferation, suggesting that STMN1 might be a therapy target for treating CSCC.

Download Full-text

Correlative cryo-ET identifies actin/tropomyosin filaments that mediate cell–substrate adhesion in cancer cells and mechanosensitivity of cell proliferation

Nature Materials ◽

10.1038/s41563-021-01087-z ◽

2021 ◽

Author(s):

Maria Lastra Cagigas ◽

Nicole S. Bryce ◽

Nicholas Ariotti ◽

Simon Brayford ◽

Peter W. Gunning ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Cells ◽

Substrate Adhesion ◽

Cell Substrate ◽

Mediate Cell ◽

Cell Substrate Adhesion

Download Full-text

Assessment of Cytotoxicity of Magnesium Oxide and Magnesium Hydroxide Nanoparticles using the Electric Cell-Substrate Impedance Sensing

Applied Sciences ◽

10.3390/app10062114 ◽

2020 ◽

Vol 10 (6) ◽

pp. 2114

Author(s):

Manishi Pallavi ◽

Jenora Waterman ◽

Youngmi Koo ◽

Jagannathan Sankar ◽

Yeoheung Yun

Keyword(s):

Magnesium Oxide ◽

Magnesium Hydroxide ◽

Bone Repair ◽

Corrosion Products ◽

Label Free ◽

Animal Testing ◽

Impedance Sensing ◽

Cell Substrate

Magnesium (Mg)-based alloys have the potential for bone repair due to their properties of biodegradation, biocompatibility, and structural stability, which can eliminate the requirement for a second surgery for the removal of the implant. Nevertheless, uncontrolled degradation rate and possible cytotoxicity of the corrosion products at the implant sites are known current challenges for clinical applications. In this study, we assessed in vitro cytotoxicity of different concentrations (0 to 50 mM) of possible corrosion products in the form of magnesium oxide (MgO) and magnesium hydroxide (Mg(OH)2) nanoparticles (NPs) in human fetal osteoblast (hFOB) 1.19 cells. We measured cell proliferation, adhesion, migration, and cytotoxicity using a real-time, label-free, non-invasive electric cell-substrate impedance sensing (ECIS) system. Our results suggest that 1 mM concentrations of MgO/Mg(OH)2 NPs are tolerable in hFOB 1.19 cells. Based on our findings, we propose the development of innovative biodegradable Mg-based alloys for further in vivo animal testing and clinical trials in orthopedics.

Download Full-text

Electric Cell-Substrate Impedance Sensing of Cellular Effects under Hypoxic Conditions and Carbonic Anhydrase Inhibition

Journal of Sensors ◽

10.1155/2017/9290478 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10

Author(s):

Luciana Stanica ◽

Mihnea Rosu-Hamzescu ◽

Mihaela Gheorghiu ◽

Miruna Stan ◽

Loredana Antonescu ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Real Time ◽

Ph Regulation ◽

Electrical Impedance Spectroscopy ◽

High Temporal Resolution ◽

Label Free ◽

Human Colon Cancer ◽

Impedance Sensing ◽

Hypoxic Conditions ◽

Cell Substrate

Tumor hypoxia provides a dynamic environment for the cancer cells to thrive and metastasize. Evaluation of cell growth, cell-cell, and cell surface interactions in hypoxic conditions is therefore highly needed in the establishment of treatment options. Electric cell-substrate impedance sensing (ECIS) has been traditionally used in the evaluation of cellular platforms as a real-time, label-free impedance-based method to study the activities of cells grown in tissue cultures, but its application for hypoxic environments is seldom reported. We present real-time evaluation of hypoxia-induced bioeffects with a focus on hypoxic pH regulation of tumor environment. To this end, multiparametric real-time bioanalytical platform using electrical impedance spectroscopy (EIS) and human colon cancer HT-29 cells is advanced. A time series of EIS data enables monitoring with high temporal resolution the alterations occurring within the cell layer, especially at the cell-substrate level. We reveal the dynamic changes of cellular processes during hypoxic conditions and in response to application of acetazolamide (AZA), a carbonic anhydrase inhibitor. Optical evaluation and pH assessment complemented the electrical analysis towards establishing a pattern of cellular changes. The proposed bioanalytical platform indicates wide applicability towards evaluation of bioeffects of hypoxia at cellular level.

Download Full-text