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Cells
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Molecular Bioelectricity and Cell Behaviour
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Molecular Bioelectricity and Cell Behaviour

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Biophysics".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 12297

Special Issue Editors

Prof. Dr. Jeremy M. Crook

E-Mail Website
Guest Editor
1. Biomedical Innovation, Chris O`Brien Lifehouse, Camperdown, NSW 2050, Australia
2. School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia
Interests: stem cell biology; cancer cell biology; neurobiology; biomaterials; electroceuticals; organoids; tissue engineering; bioprinting; regenerative medicine
Special Issues, Collections and Topics in MDPI journals
Dr. Eva Tomaskovic-Crook

E-Mail Website
Guest Editor
ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, Wollongong 2500, Australia
Interests: stem cell biology; cancer cell biology; neurobiology; biomaterials; electroceuticals; organoids; tissue engineering; bioprinting; regenerative medicine; gene and molecular therapy

Special Issue Information

Dear Colleagues,

Molecular bioelectricity is an emerging discipline that exploits endogenous electrically mediated signalling for understanding and controlling cell behaviours. First explicated in the 1800s by physicist and biologist Luigi Galvani who investigated “animal electricity”, it also derives from the work of Lionel Jaffe in the 1970s, which prompted new research into the role of electrical currents in cell and tissue development, tissue regeneration, and cancer therapeutics. It is now clear that electrical potential is essential to the function of all cells, being both a by-product and regulator of diverse inter- and intra-cellular processes, in parallel and in series with biochemical (including transcriptional) and physicochemical signalling. Notwithstanding the considerable and compelling work on biological electrical phenomena to date, Molecular Bioelectricity remains relatively understudied and underutilised, with significant potential for frontier research and biomedical innovation. In this Special Issue of Cells, we would like to present advances in the fundamental understanding of the coupling between human cell physiology and bioelectricity, extending to pathophysiology, with the latter including but not limited to disorders of development, cancer, and tissue trauma. Additionally, we are interested in the translation of bioelectrics for diagnostics and therapeutics, again including but not limited to cancer therapeutics, regenerative medicine, and disorders of development. 

Guest Editors
Jeremy Micah Crook and Eva Tomaskovic-Crook

Prof. Dr. Jeremy M. Crook
Dr. Eva Tomaskovic-Crook
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bioelectricity
  • ions
  • charged molecule
  • cell behavior
  • development
  • disease
  • cancer
  • regenerative medicine
  • diagnostics
  • therapeutics

Published Papers (4 papers)

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Research

15 pages, 5589 KiB  
Article
Zebrafish Embryos Display Characteristic Bioelectric Signals during Early Development
by Martin R. Silic, Ziyu Dong, Yueyi Chen, Adam Kimbrough and Guangjun Zhang
Cells 2022, 11(22), 3586; https://doi.org/10.3390/cells11223586 - 12 Nov 2022
Cited by 3 | Viewed by 2459
Abstract
Bioelectricity is defined as endogenous electrical signaling mediated by the dynamic distribution of charged molecules. Recently, increasing evidence has revealed that cellular bioelectric signaling is critical for regulating embryonic development, regeneration, and congenital diseases. However, systematic real-time in vivo dynamic electrical activity monitoring [...] Read more.
Bioelectricity is defined as endogenous electrical signaling mediated by the dynamic distribution of charged molecules. Recently, increasing evidence has revealed that cellular bioelectric signaling is critical for regulating embryonic development, regeneration, and congenital diseases. However, systematic real-time in vivo dynamic electrical activity monitoring of whole organisms has been limited, mainly due to the lack of a suitable model system and voltage measurement tools for in vivo biology. Here, we addressed this gap by utilizing a genetically stable zebrafish line, Tg (ubiquitin: ASAP1), and ASAP1 (Accelerated sensor of action potentials 1), a genetically encoded voltage indicator (GEVI). With light-sheet microscopy, we systematically investigated cell membrane potential (Vm) signals during different embryonic stages. We found cells of zebrafish embryos showed local membrane hyperpolarization at the cleavage furrows during the cleavage period of embryogenesis. This signal appeared before cytokinesis and fluctuated as it progressed. In contrast, whole-cell transient hyperpolarization was observed during the blastula and gastrula stages. These signals were generally limited to the superficial blastomere, but they could be detected within the deeper cells during the gastrulation period. Moreover, the zebrafish embryos exhibit tissue-level cell Vm signals during the segmentation period. Middle-aged somites had strong and dynamic Vm fluctuations starting at about the 12-somite stage. These embryonic stage-specific characteristic cellular bioelectric signals suggest that they might play a diverse role in zebrafish embryogenesis that could underlie human congenital diseases. Full article
(This article belongs to the Special Issue Molecular Bioelectricity and Cell Behaviour)
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16 pages, 3106 KiB  
Article
Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging
by Hoa T. Le, Michael Staelens, Davide Lazzari, Gordon Chan and Jack A. Tuszyński
Cells 2022, 11(17), 2712; https://doi.org/10.3390/cells11172712 - 31 Aug 2022
Cited by 1 | Viewed by 2722
Abstract
The effects of electric fields (EFs) on various cell types have been thoroughly studied, and exhibit a well-known regulatory effect on cell processes, implicating their usage in several medical applications. While the specific effect exerted on cells is highly parameter-dependent, the majority of [...] Read more.
The effects of electric fields (EFs) on various cell types have been thoroughly studied, and exhibit a well-known regulatory effect on cell processes, implicating their usage in several medical applications. While the specific effect exerted on cells is highly parameter-dependent, the majority of past research has focused primarily on low-frequency alternating fields (<1 kHz) and high-frequency fields (in the order of MHz). However, in recent years, low-intensity (1–3 V/cm) alternating EFs with intermediate frequencies (100–500 kHz) have been of topical interest as clinical treatments for cancerous tumours through their disruption of cell division and the mitotic spindle, which can lead to cell death. These aptly named tumour-treating fields (TTFields) have been approved by the FDA as a treatment modality for several cancers, such as malignant pleural mesothelioma and glioblastoma multiforme, demonstrating remarkable efficacy and a high safety profile. In this work, we report the results of in vitro experiments with HeLa and MCF-10A cells exposed to TTFields for 18 h, imaged in real time using live-cell imaging. Both studied cell lines were exposed to 100 kHz TTFields with a 1-1 duty cycle, which resulted in significant mitotic and cytokinetic arrest. In the experiments with HeLa cells, the effects of the TTFields’ frequency (100 kHz vs. 200 kHz) and duty cycle (1-1 vs. 1-0) were also investigated. Notably, the anti-mitotic effect was stronger in the HeLa cells treated with 100 kHz TTFields. Additionally, it was found that single and two-directional TTFields (oriented orthogonally) exhibit a similar inhibitory effect on HeLa cell division. These results provide real-time evidence of the profound ability of TTFields to hinder the process of cell division by significantly delaying both the mitosis and cytokinesis phases of the cell cycle. Full article
(This article belongs to the Special Issue Molecular Bioelectricity and Cell Behaviour)
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22 pages, 6182 KiB  
Article
Screening Biophysical Sensors and Neurite Outgrowth Actuators in Human Induced-Pluripotent-Stem-Cell-Derived Neurons
by Vaibhav P. Pai, Ben G. Cooper and Michael Levin
Cells 2022, 11(16), 2470; https://doi.org/10.3390/cells11162470 - 09 Aug 2022
Cited by 2 | Viewed by 3008
Abstract
All living cells maintain a charge distribution across their cell membrane (membrane potential) by carefully controlled ion fluxes. These bioelectric signals regulate cell behavior (such as migration, proliferation, differentiation) as well as higher-level tissue and organ patterning. Thus, voltage gradients represent an important [...] Read more.
All living cells maintain a charge distribution across their cell membrane (membrane potential) by carefully controlled ion fluxes. These bioelectric signals regulate cell behavior (such as migration, proliferation, differentiation) as well as higher-level tissue and organ patterning. Thus, voltage gradients represent an important parameter for diagnostics as well as a promising target for therapeutic interventions in birth defects, injury, and cancer. However, despite much progress in cell and molecular biology, little is known about bioelectric states in human stem cells. Here, we present simple methods to simultaneously track ion dynamics, membrane voltage, cell morphology, and cell activity (pH and ROS), using fluorescent reporter dyes in living human neurons derived from induced neural stem cells (hiNSC). We developed and tested functional protocols for manipulating ion fluxes, membrane potential, and cell activity, and tracking neural responses to injury and reinnervation in vitro. Finally, using morphology sensor, we tested and quantified the ability of physiological actuators (neurotransmitters and pH) to manipulate nerve repair and reinnervation. These methods are not specific to a particular cell type and should be broadly applicable to the study of bioelectrical controls across a wide range of combinations of models and endpoints. Full article
(This article belongs to the Special Issue Molecular Bioelectricity and Cell Behaviour)
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22 pages, 2954 KiB  
Article
The Cardiac Ryanodine Receptor Provides a Suitable Pathway for the Rapid Transport of Zinc (Zn2+)
by Jana Gaburjakova and Marta Gaburjakova
Cells 2022, 11(5), 868; https://doi.org/10.3390/cells11050868 - 03 Mar 2022
Cited by 5 | Viewed by 2492
Abstract
The sarcoplasmic reticulum (SR) in cardiac muscle is suggested to act as a dynamic storage for Zn2+ release and reuptake, albeit it is primarily implicated in the Ca2+ signaling required for the cardiac cycle. A large Ca2+ release from the [...] Read more.
The sarcoplasmic reticulum (SR) in cardiac muscle is suggested to act as a dynamic storage for Zn2+ release and reuptake, albeit it is primarily implicated in the Ca2+ signaling required for the cardiac cycle. A large Ca2+ release from the SR is mediated by the cardiac ryanodine receptor (RYR2), and while this has a prominent conductance for Ca2+ in vivo, it also conducts other divalent cations in vitro. Since Zn2+ and permeant Mg2+ have similar physical properties, we tested if the RYR2 channel also conducts Zn2+. Using the method of planar lipid membranes, we evidenced that the RYR2 channel is permeable to Zn2+ with a considerable conductance of 81.1 ± 2.4 pS, which was significantly lower than the values for Ca2+ (127.5 ± 1.8 pS) and Mg2+ (95.3 ± 1.4 pS), obtained under the same asymmetric conditions. Despite similar physical properties, the intrinsic Zn2+ permeability (PCa/PZn = 2.65 ± 0.19) was found to be ~2.3-fold lower than that of Mg2+ (PCa/PMg = 1.146 ± 0.071). Further, we assessed whether the channel itself could be a direct target of the Zn2+ current, having the Zn2+ finger extended into the cytosolic vestibular portion of the permeation pathway. We attempted to displace Zn2+ from the RYR2 Zn2+ finger to induce its structural defects, which are associated with RYR2 dysfunction. Zn2+ chelators were added to the channel cytosolic side or strongly competing cadmium cations (Cd2+) were allowed to permeate the RYR2 channel. Only the Cd2+ current was able to cause the decay of channel activity, presumably as a result of Zn2+ to Cd2+ replacement. Our findings suggest that the RYR2 channel can provide a suitable pathway for rapid Zn2+ escape from the cardiac SR; thus, the channel may play a role in local and/or global Zn2+ signaling in cardiomyocytes. Full article
(This article belongs to the Special Issue Molecular Bioelectricity and Cell Behaviour)
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