Integration of electrotaxis and durotaxis in cancer cells: Subtle nonlinear responses to electromechanical coupling cues

Yang, Qunfeng; Jiang, Nan; Xu, Hongwei; Zhang, Yajun; Xiong, Chunyang; Huang, Jianyong

doi:10.1016/j.bios.2021.113289

Cited by 5 publications

(8 citation statements)

References 61 publications

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“…[ 32,34,35 ] To characterize the time‐related process of cell invasion/migration in the 3D extracellular matrices, we introduced an equivalent circuit model including a series of key electrical elements (Figure 3A,B). In the model, the resistance of cell culture media was denoted as R ccm , which was essentially a function of the total ion concentration in the media and ambient temperature, [ 10,36 ] whereas the interfacial effect between the interdigitated electrodes and the media that behaved as electrolytes, was modeled as a constant phase angle impedance Z CPA in parallel with a charge transfer resistance R ct , which characterized the interface capacitance impedance and the capability of the electrodes to participate in exchange current reactions, respectively. [ 37,38 ] Specifically, the constant phase angle impedance could be quantitatively expressed as

\begin{equation}{Z}_{{\rm{CPA}}}\left( {\omega ,Q,n} \right) = \frac{1}{{Q{{\left( {j\omega } \right)}}^n}}\end{equation}

where Q denoted the magnitude of Z CPA , n was a constant with 0 ≤ n ≤ 1 that characterized the inhomogeneities of the electrode surfaces, ω was the angular frequency, and j stood for the imaginary unit.…”

Section: Resultsmentioning

confidence: 99%

High‐Throughput Electromechanical Coupling Chip Systems for Real‐Time 3D Invasion/Migration Assay of Cells

Jiang

Han

et al. 2023

Advanced Science

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Cell invasion/migration through three‐dimensional (3D) tissues is not only essential for physiological/pathological processes, but a hallmark of cancer malignancy. However, how to quantify spatiotemporal dynamics of 3D cell migration/invasion is challenging. Here, this work reports a 3D cell invasion/migration assay (3D‐CIMA) based on electromechanical coupling chip systems, which can monitor spatiotemporal dynamics of 3D cell invasion/migration in a real‐time, label‐free, nondestructive, and high‐throughput way. In combination with 3D topological networks and complex impedance detection technology, this work shows that 3D‐CIMA can quantitively characterize collective invasion/migration dynamics of cancer cells in 3D extracellular matrix (ECM) with controllable biophysical/biomechanical properties. More importantly, this work further reveals that it has the capability to not only carry out quantitative evaluation of anti‐tumor drugs in 3D microenvironments that minimize the impact of cell culture dimensions, but also grade clinical cancer specimens. The proposed 3D‐CIMA offers a new quantitative methodology for investigating cell interactions with 3D extracellular microenvironments, which has potential applications in various fields like mechanobiology, drug screening, and even precision medicine.

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\begin{equation}{Z}_{{\rm{CPA}}}\left( {\omega ,Q,n} \right) = \frac{1}{{Q{{\left( {j\omega } \right)}}^n}}\end{equation}

Section: Resultsmentioning

confidence: 99%

High‐Throughput Electromechanical Coupling Chip Systems for Real‐Time 3D Invasion/Migration Assay of Cells

Jiang

Han

et al. 2023

Advanced Science

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“…Until now, space-time distributions of E f are neither experimentally nor theoretically known. In this study, E f represents the active bioelectricity of unperturbed cancer and due to endogenous electrical biopotentials (ϕ) and/or intrinsic electrical sources in it [8,9,[14][15][16][19][20][21][22][23][24][25][26]. Miklavcǐčet al [44] measure experimentally ϕ along axial (z-axis) and radial (r-axis) directions in two tumour types (LLC and fibrosarcoma Sa-1).…”

Section: Further Comments About Assumptions 1 4 Andmentioning

confidence: 99%

“…Electrically active cancer cells possess bioelectric circuitry that generates resting membrane potential and endogenous electric fields that influence cell functions and communication [8,23]. Endogenous electric potential gradients (established across multiple cells due to gap junctions and other cell-to-cell connections on a tissue level) induce small endogenous electric fields, which are responsible for altered migration and invasiveness of cancer cells [18,24].…”

Section: Introductionmentioning

confidence: 99%

Simulations of surface charge density changes during the untreated solid tumour growth

et al. 2022

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Understanding untreated tumour growth kinetics and its intrinsic behaviour is interesting and intriguing. The aim of this study is to propose an approximate analytical expression that allows us to simulate changes in surface charge density at the cancer-surrounding healthy tissue interface during the untreated solid tumour growth. For this, the Gompertz and Poisson equations are used. Simulations reveal that the unperturbed solid tumour growth is closely related to changes in the surface charge density over time between the tumour and the surrounding healthy tissue. Furthermore, the unperturbed solid tumour growth is governed by temporal changes in this surface charge density. It is concluded that results corroborate the correspondence between the electrical and physiological parameters in the untreated cancer, which may have an essential role in its growth, progression, metastasis and protection against immune system attack and anti-cancer therapies. In addition, the knowledge of surface charge density changes at the cancer-surrounding healthy tissue interface may be relevant when redesigning the molecules in chemotherapy and immunotherapy taking into account their polarities. This can also be true in the design of completely novel therapies.

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“…[14] Given the urgency of biofilm-associated infections in the post-antibiotic era, there is an urgent need to develop a more suitable in vitro AST model to determine the minimum biofilm elimination concentration (MBEC) in 3D confined ECM with specific physiological rigidities. [15,16] Essentially, the morphological evolution of bacterial biofilms/ microcolonies is directly related to ECM rigidities, [7] which generally vary from 0.5 to 20 kPa in human tissues, [17] depending on specific tissues and their pathophysiological states. In general, the higher the Young's modulus of ECM, the stronger its confinement ability to 3D bacterial biofilms/microcolonies.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Matrix Rigidities Regulate the Tricarboxylic Acid Cycle and Antibiotic Resistance of Three‐Dimensionally Confined Bacterial Microcolonies

Han

Jiang

et al. 2023

Advanced Science

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As a major cause of clinical chronic infection, microbial biofilms/microcolonies in host tissues essentially live in 3D‐constrained microenvironments, which potentially modulate their spatial self‐organization and morphodynamics. However, it still remains unclear whether and how mechanical cues of 3D confined microenvironments, for example, extracellular matrix (ECM) stiffness, exert an impact on antibiotic resistance of bacterial biofilms/microcolonies. With a high‐throughput antibiotic sensitivity testing (AST) platform, it is revealed that 3D ECM rigidities greatly modulate their resistance to diverse antibiotics. The microcolonies in 3D ECM with human tissue‐specific rigidities varying from 0.5 to 20 kPa show a ≈2–10 000‐fold increase in minimum inhibitory concentration, depending on the types of antibiotics. The authors subsequently identified that the increase in 3D ECM rigidities leads to the downregulation of the tricarboxylic acid (TCA) cycle, which is responsible for enhanced antibiotic resistance. Further, it is shown that fumarate, as a potentiator of TCA cycle activity, can alleviate the elevated antibiotic resistance and thus remarkably improve the efficacy of antibiotics against bacterial microcolonies in 3D confined ECM, as confirmed in the chronic infection mice model. These findings suggest fumarate can be employed as an antibiotic adjuvant to effectively treat infections induced by bacterial biofilms/microcolonies in a 3D‐confined environment.

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Integration of electrotaxis and durotaxis in cancer cells: Subtle nonlinear responses to electromechanical coupling cues

Cited by 5 publications

References 61 publications

High‐Throughput Electromechanical Coupling Chip Systems for Real‐Time 3D Invasion/Migration Assay of Cells

High‐Throughput Electromechanical Coupling Chip Systems for Real‐Time 3D Invasion/Migration Assay of Cells

Simulations of surface charge density changes during the untreated solid tumour growth

Extracellular Matrix Rigidities Regulate the Tricarboxylic Acid Cycle and Antibiotic Resistance of Three‐Dimensionally Confined Bacterial Microcolonies

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