Physical modelling of electroporation in close cell-to-cell proximity environments

Gaynor, Paul; Bodger, P.S.

doi:10.1088/0031-9155/51/12/012

Cited by 9 publications

(3 citation statements)

References 36 publications

(93 reference statements)

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“…The ion concentration gradient between outside and inside of the cellular membrane generates a resting potential difference, which is homogenous all along the cell membrane. 29 Upon application of voltage, such electric potential difference across the cellular membrane will disrupt the field lines, 30,31 consequently, leading to the current forced to flow around the cell and forming the ionic layers along the cellular membrane. The largest field line distortion is recognized at the sides of the membrane facing the field lines.…”

Section: Working Principles Of Multi-directional Electric Field Scannmentioning

confidence: 99%

3D-printing Enabled Micro-assembly of Microfluidic Electroporation System for 3D Tissue Engineering

Zhu

Hamilton

2019

Preprint

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Electro-transfection is an essential workhorse tool for regulating cellular responses and engineering cellular materials in tissue engineering. However, existing approaches, including microfluidic platforms and bench top methods, are only able to study monolayer cell suspensions in vitro, and are incapable of clinical translation within in vivo tissue microenvironment.Knowledge regarding the three-dimensional (3D) electric field distribution and mass transport in a tissue microenvironment is lacking. However, building a 3D electro-transfection system that is compatible with 3D cell culture for mimicking in vivo tissue microenvironment is challenging, due to the substantial difficulties in control of 3D electric field distribution as well as the cellular growth. To address such challenges, we introduce a novel 3D micro-assembling strategy assisted by 3D printing, which enables the molding of 3D microstructures as LEGO® parts from 3D-printed molds. The molded PDMS LEGO  bricks are then assembled into a 3D-cell culture chamber interconnected with vertical and horizontal perfusion microchannels as a 3D channel network. Such 3D perfusion microchannel network is unattainable by direct 3D printing or other microfabrication approaches, which can facilitate the high-efficient exchange of nutrition and waste for 3D cell growth.Four flat electrodes are mounted into the 3D culture chamber via a 3D-printed holder and controlled by a programmable power sequencer for multi-directional electric frequency scanning (3D -electro-transfection). This multi-directional scanning not only can create transient pores all over the cell membrane, but also can generate local oscillation for enhancing mass transport and improving cell transfection efficiency. As a proof-of-concept, we electro-delivered pAcGFP1-C1 vector to 3D cultured HeLa cells within peptide hydrogel scaffolding. The expressed GFP level from transfected HeLa cells reflects the transfection efficiency. We found two key parameters including electric field strength and plasmid concentration playing more important roles than manipulating pulse duration and duty cycles. The results showed an effective transfection efficiency of ~15% with ~85% cell viability, which is a 3-fold increase compared to the conventional benchtop 3D cell transfection. This 3D -electrotransfection system was further used for genetically editing 3D-cultured Hek-293 cells via direct delivery of CRISPR/Cas9 plasmid which showed successful transfection with GFP expressed in the cytoplasm as the reporter. The 3D-printing enabled micro-assembly allows facile creation of novel 3D culture system for electro-transfection which can be employed for versatile gene delivery and cellular engineering, as well as building in-vivo like tissue models for fundamentally studying cellular regulatory mechanisms. the orientation of cells to the electric fields and so on. [16][17] Thus, the clinical in vivo gene delivery faces tremendous problems. 3,18 Although the in vitro cellular spheroid model is often applied to study t...

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Section: Working Principles Of Multi-directional Electric Field Scannmentioning

confidence: 99%

3D-printing Enabled Micro-assembly of Microfluidic Electroporation System for 3D Tissue Engineering

Zhu

Hamilton

2019

Preprint

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“…In 2007, Pavlin et al 11 extended that work and presented a quantitative explanation for their measurements in terms of a detailed model based on the creation of two types of pores: transient pores, open only during the application of the electric field and long-lived "transport pores." Gaynor and Bodger 12 used their "balloon model" to simulate electrical effects of cellcell interactions in the electroporation process. In that work, spherical latex membranes were used to simulate cells; various two-cell, "couplet" arrangements and a 3 Â 3 Â 3 simple cubic lattice of "cells" were studied.…”

Section: Introductionmentioning

confidence: 99%

Cell-cell proximity effects in multi-cell electroporation

Henslee

Morss

et al. 2014

Biomicrofluidics

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We report a fundamental study of how the electropermeabilization of a cell is affected by nearby cells. Previous researchers studying electroporation of dense suspensions of cells have observed, both theoretically and experimentally, that such samples cannot be treated simply as collections of independent cells. However, the complexity of those systems makes quantitative modeling difficult. We studied the change in the minimum applied electric field, the threshold field, required to affect electropermeabilization of a cell due to the presence of a second cell. Experimentally, we used optical tweezers to accurately position two cells in a custom fluidic electroporation device and measured the threshold field for electropermeabilization. We also captured video of the process. In parallel, finite element simulations of the electrostatic potential distributions in our systems were generated using the 3-layer model and the contact resistance methods. Reasonably good agreement with measurements was found assuming a model in which changes in a cell's threshold field were predicted from the calculated changes in the maximum voltage across the cell's membrane induced by the presence of a second cell. The threshold field required to electroporate a cell is changed $5%-10% by a nearby, nearly touching second cell. Cells aligned parallel to the porating field shield one another. Those oriented perpendicular to the field enhance the applied field's effect. In addition, we found that the dynamics of the electropermeabilization process are important in explaining observations for even our simple two-cell system. V C 2014 AIP Publishing LLC. [http://dx

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“…The purpose of this note is to analyse an electroporation (Weaver and Chimadzhev 1996, Gaynor and Bodger 2006, Vernier et al 2006, Pliquett et al 2007, Chen et al 2008, Granot et al 2009, Levine and Vernier 2010) method which avoids the need to insert electrodes into tumour regions, as is current practice in cancer treatment (Hoffmann et al 1999, Mir 2000, Gothelf et al 2003, Sersa et al 2008. The required high electric fields are provided by external electrodes, and amplified within the patient's body by elongated micro-conductors.…”

Section: Introductionmentioning

confidence: 99%

Electroporation in cancer therapy without insertion of electrodes

Lekner

2014

Phys. Med. Biol.

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Electroporation in cancer therapy in which elongated micron-sized conductors are used to enhance an externally applied electric field is investigated. Such field enhancement was previously used in carbon and boron nitride nanotube electropermeabilization. It is envisaged that the micro-conductors would be injected together with therapeutic drugs into tumorous regions, and a pulsed or alternating external field would be applied. Amplification of this external electric field at the pointed ends of the elongated micro-conductors would then give (locally) a field sufficiently large to cause electroporation. The torque of the electric field on the polarized micro-conductors will tend to align them with the field, giving the configuration of maximum field enhancement at their ends. Brownian (thermal) motion will disrupt this alignment. We give an analysis of field enhancement, torque, and thermal motion for micro-conductors of prolate spheroidal shape, and estimate the range of their size for use in human tissue.

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Physical modelling of electroporation in close cell-to-cell proximity environments

Cited by 9 publications

References 36 publications

3D-printing Enabled Micro-assembly of Microfluidic Electroporation System for 3D Tissue Engineering

3D-printing Enabled Micro-assembly of Microfluidic Electroporation System for 3D Tissue Engineering

Cell-cell proximity effects in multi-cell electroporation

Electroporation in cancer therapy without insertion of electrodes

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