Cellular response to high pulse repetition rate nanosecond pulses varies with fluorescent marker identity

Steelman, Zachary A.; Tolstykh, Gleb P.; Beier, Hope T.; Ibey, Bennett L.

doi:10.1016/j.bbrc.2016.08.107

Cited by 33 publications

(26 citation statements)

References 28 publications

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“…We confirmed that U87 cells undergo plasma membrane permeabilisation following the delivery of nsPEF and that, as previously reported, the extent and rapidity of poration increases with increasing pulse numbers18 and application frequency30. Using live-cell imaging we demonstrated that permeabilisation does not occur across the entire cell membrane, as YO-PRO-1 showed a polar entry and then diffused across the cell, in agreement with a previous study using 600 ns pulses31.…”

Section: Discussionsupporting

confidence: 92%

Calcium-independent disruption of microtubule dynamics by nanosecond pulsed electric fields in U87 human glioblastoma cells

Carr

Bardet

Burke

et al. 2017

Sci Rep

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High powered, nanosecond duration, pulsed electric fields (nsPEF) cause cell death by a mechanism that is not fully understood and have been proposed as a targeted cancer therapy. Numerous chemotherapeutics work by disrupting microtubules. As microtubules are affected by electrical fields, this study looks at the possibility of disrupting them electrically with nsPEF. Human glioblastoma cells (U87-MG) treated with 100, 10 ns, 44 kV/cm pulses at a frequency of 10 Hz showed a breakdown of their interphase microtubule network that was accompanied by a reduction in the number of growing microtubules. This effect is temporally linked to loss of mitochondrial membrane potential and independent of cellular swelling and calcium influx, two factors that disrupt microtubule growth dynamics. Super-resolution microscopy revealed microtubule buckling and breaking as a result of nsPEF application, suggesting that nsPEF may act directly on microtubules.

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Section: Discussionsupporting

confidence: 92%

Calcium-independent disruption of microtubule dynamics by nanosecond pulsed electric fields in U87 human glioblastoma cells

Carr

Bardet

Burke

et al. 2017

Sci Rep

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“…An alternative hypothesis is that a subcellular process becomes saturated by the ↑900 nsEP, but exposure to the ↑300 nsEP allows further subcellular cascade activation potentiating YO-PRO®-1 uptake. Additionally, while some attention has been paid to the frequency components of BP versus UP pulses, this large difference between the effects driven by the ↑300↓900 and ↑900↓300 BP nsEP exposures would appear to reduce the likelihood that frequency components within each pulse are playing a dominant role 6 , 12 , 13 , 15 .…”

Section: Discussionmentioning

confidence: 99%

Asymmetrical bipolar nanosecond electric pulse widths modify bipolar cancellation

Valdez

Barnes

Roth

et al. 2017

Sci Rep

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A bipolar (BP) nanosecond electric pulse (nsEP) exposure generates reduced calcium influx compared to a unipolar (UP) nsEP. This attenuated physiological response from a BP nsEP exposure is termed “bipolar cancellation” (BPC). The predominant BP nsEP parameters that induce BPC consist of a positive polarity (↑) front pulse followed by the delivery of a negative polarity (↓) back pulse of equal voltage and width; thereby the duration is twice a UP nsEP exposure. We tested these BPC parameters, and discovered that a BP nsEP with symmetrical pulse widths is not required to generate BPC. For example, our data revealed the physiological response initiated by a ↑900 nsEP exposure can be cancelled by a second pulse that is a third of its duration. However, we observed a complete loss of BPC from a ↑300 nsEP followed by a ↓900 nsEP exposure. Spatiotemporal analysis revealed these asymmetrical BP nsEP exposures generate distinct local YO-PRO®-1 uptake patterns across the plasma membrane. From these findings, we generated a conceptual model that suggests BPC is a phenomenon balanced by localized charging and discharging events across the membrane.

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“…It was found that when 10 and 20 of these pulses were applied, permeabilization of the vesicles, but also permeabilization of the plasma membrane, occurred [Napotnik et al, ]. The differing results in the two studies indicate that the degree of the outer membrane permeabilization to that of subcellular membranes depends not just on cell type but might be affected, and therefore controlled, by the choice of pulse parameters, such as pulse duration, pulse rise time, pulse amplitude, pulse number, and even pulse repetition rate [Steelman et al, ].…”

Section: Primary Effects Of Ultrashort Pulses On Cellsmentioning

confidence: 99%

“…On the other hand, if thermal effects can be excluded by limiting the number of pulses, varying the repetition rate of nanosecond pulses might allow us to explore and possibly control the uptake of molecules. This has been shown by recording the uptake of Propidium Iodide, FM 1–43, and YO‐PRO‐1 in CHO‐K1 cells over a range of pulse repetition frequency from 5 Hz to 500 kHz [Steelman et al, ]. However, even without taking the effect of pulse frequency into account, the electrical parameters of the pulse, duration, rise time and amplitude, and the pulse number cover a wide range.…”

Section: Scaling Of Nanosecond Pulse Effectsmentioning

confidence: 99%

From the basic science of biological effects of ultrashort electrical pulses to medical therapies

Schoenbach

2018

Bioelectromagnetics

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This article is based on my presentation at the D'Arsonval Ceremony at the Joint Annual Meeting of the Bioelectromagnetics Society and the European BioElectromagnetics Association in Hangzhou, China, in June of 2017. It describes the pathway from the first studies on the effects of intense, nanosecond pulses on biological cells to the development of medical therapies based on these effects. The motivation for the initial studies of the effects of high voltage, nanosecond pulses on mammalian cells was based on a simple electrical circuit model, which predicted that such pulses allow us to affect not just the plasma membrane but also the subcellular structures. The first experimental study that confirmed this hypothesis was published in 2001 in the Bioelectromagnetics journal. It was followed by a large number of publications that showed that such ultrashort pulses affect cell functions, such as programmed cell death, and, at lower intensity, calcium mobilization from intracellular structures. These basic studies were leading to novel cancer treatments, treatments of cardiac arrhythmia, and advanced wound healing. Further, by reducing the pulse duration into the picosecond range, antenna-based neural stimulation seems to be possible. This manuscript gives an overview of the progress in this field of research in the decade after the initial bioelectric studies with high-voltage, nanosecond pulses, particularly the research performed at the Frank Reidy Research Center for Bioelectrics. It also tells you about my journey and that of my colleagues at the Center for Bioelectrics into and through this fascinating bioelectromagnetics research area. Bioelectromagnetics. 39:257-276, 2018. © 2018 Wiley Periodicals, Inc.

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Cellular response to high pulse repetition rate nanosecond pulses varies with fluorescent marker identity

Cited by 33 publications

References 28 publications

Calcium-independent disruption of microtubule dynamics by nanosecond pulsed electric fields in U87 human glioblastoma cells

Calcium-independent disruption of microtubule dynamics by nanosecond pulsed electric fields in U87 human glioblastoma cells

Asymmetrical bipolar nanosecond electric pulse widths modify bipolar cancellation

From the basic science of biological effects of ultrashort electrical pulses to medical therapies

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