Single-Cell Mechanophenotyping in Microfluidics to Evaluate Behavior of U87 Glioma Cells

Sengul, Esra; Elitaş, Meltem

doi:10.3390/mi11090845

Cited by 11 publications

(9 citation statements)

References 53 publications

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“…A precise and accurate characterization of cells in the GBM microenvironment will lead better diagnosis, prognosis, and personalized treatment strategies [9][10][11][12][13]. In literature, there is still a lack of quantification about electrical and mechanical properties of glioma cells at single-cell level [16,19,27,[29][30][31]. In this context, Memmel and co-workers reported the migration pattern, actin cytoskeleton organization, and response to PI1K-, mTOR-, and Hsp90-inhibition of glioblastoma cells with different invasive capacities.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have demonstrated effective tools to investigate mostly mechanical properties of glioma cells using fluorescence microscopy [15][16][17][18][19][20][21][22][23][24][25][26][27], 2-photon imaging [11,28], atomic force microscopy [16,29,30], single-cell force spectroscopy [16], and microfluidic technologies [31][32][33][34][35][36][37][38][39]. In contrast to mechanical features, electrical properties of glioma cells have not been extensively interrogated.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of U87 glioma cells by dielectrophoresis

et al. 2022

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Glioblastoma multiforme is the most aggressive and invasive brain cancer consisting of genetically and phenotypically altering glial cells. It has massive heterogeneity due to its highly complex and dynamic microenvironment. Here, electrophysiological properties of U87 human glioma cell line were measured based on a dielectrophoresis phenomenon to quantify the population heterogeneity of glioma cells. Dielectrophoretic forces were generated using a gold‐microelectrode array within a microfluidic channel when 3 Vpp and 100, 200, 300, 400, 500 kHz, 1, 2, 5, and 10 MHz frequencies were applied. We analyzed the dielectrophoretic behavior of 500 glioma cells, and revealed that the crossover frequency of glioma cells was around 140 kHz. A quantifying dielectrophoretic movement of the glioma cells exhibited three distinct glioma subpopulations: 50% of the glioma cells experienced strong, 30% of the cells were spread in the microchannel by moderate, and the rest of the cells experienced very weak positive dielectrophoretic forces. Our results demonstrated the dielectrophoretic spectra of U87 glioma cell line. Dielectrophoretic responses of glioma cells linked population heterogeneity to membrane properties of glioma cells rather than their size distribution in the population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analysis of U87 glioma cells by dielectrophoresis

et al. 2022

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“…Unique mechanical properties of glioma and its microenvironment provide a basis for the development of novel diagnostics to address two unmet needs in clinical medicine: 1) accurate identification of infiltrative disease in nervous tissue that is radiographically and microscopically occult and 2) characterization disease heterogeneity and plasticity towards predictive analytics for treatment response or prognosis. Fundamental technologies are available as were described in the studies presented in this review such as MRE and other tools for rheological phenotyping, and these have the potential to be adapted and refined as possible intraoperative adjuncts or as supplements to the conventional imaging obtained for patients with GBM to better guide treatment choices (57,59,61,62,67,(152)(153)(154). Briefly, techniques can be categorized based on the substrate assessed-either cells and tissue or more macroscopically a region of the brain (Table 2).…”

Section: Diagnosticsmentioning

confidence: 99%

“…Comprehensive reviews of methodologies used to study mechanical properties in vitro and in vivo can be found elsewhere (47,85,155). Advances in bioengineering in the fields of microfluidics, biomimetics, and hydrogel may also enable the development of high-throughput, point-of-care methods to define disease features such as the mechanophenotype that may aid in clinical-decision making (84,147,152,157).…”

Section: Diagnosticsmentioning

confidence: 99%

Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities

et al. 2022

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Gliomas represent the most common malignant primary brain tumors, and a high-grade subset of these tumors including glioblastoma are particularly refractory to current standard-of-care therapies including maximal surgical resection and chemoradiation. The prognosis of patients with these tumors continues to be poor with existing treatments and understanding treatment failure is required. The dynamic interplay between the tumor and its microenvironment has been increasingly recognized as a key mechanism by which cellular adaptation, tumor heterogeneity, and treatment resistance develops. Beyond ongoing lines of investigation into the peritumoral cellular milieu and microenvironmental architecture, recent studies have identified the growing role of mechanical properties of the microenvironment. Elucidating the impact of these biophysical factors on disease heterogeneity is crucial for designing durable therapies and may offer novel approaches for intervention and disease monitoring. Specifically, pharmacologic targeting of mechanical signal transduction substrates such as specific ion channels that have been implicated in glioma progression or the development of agents that alter the mechanical properties of the microenvironment to halt disease progression have the potential to be promising treatment strategies based on early studies. Similarly, the development of technology to measure mechanical properties of the microenvironment in vitro and in vivo and simulate these properties in bioengineered models may facilitate the use of mechanical properties as diagnostic or prognostic biomarkers that can guide treatment. Here, we review current perspectives on the influence of mechanical properties in glioma with a focus on biophysical features of tumor-adjacent tissue, the role of fluid mechanics, and mechanisms of mechanical signal transduction. We highlight the implications of recent discoveries for novel diagnostics, therapeutic targets, and accurate preclinical modeling of glioma.

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“…The same group [ 33 ] investigated the impact of macrophages on glioma cell behavior by using a microfabricated cell culture platform. They quantified motility, migration, morphology, proliferation, and deformation characteristics of glioma U87 cells at the single-cell resolution to unveil biomechanical heterogeneity.…”

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confidence: 99%