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Single-cell mechanical analysis reveals viscoelastic similarities between normal and neoplastic brain cells
Understanding cancer cell mechanics allows for the identification of novel disease mechanisms, diagnostic biomarkers, and targeted therapies. In this study, we utilized our previously established fluid shear stress assay to investigate and compare the viscoelastic properties of normal immortalized h...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557591/ https://www.ncbi.nlm.nih.gov/pubmed/37808779 http://dx.doi.org/10.1101/2023.09.23.559055 |
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author | Onwudiwe, Killian Najera, Julian Holen, Luke Burchett, Alice A. Rodriguez, Dorielis Zarodniuk, Maksym Siri, Saeed Datta, Meenal |
author_facet | Onwudiwe, Killian Najera, Julian Holen, Luke Burchett, Alice A. Rodriguez, Dorielis Zarodniuk, Maksym Siri, Saeed Datta, Meenal |
author_sort | Onwudiwe, Killian |
collection | PubMed |
description | Understanding cancer cell mechanics allows for the identification of novel disease mechanisms, diagnostic biomarkers, and targeted therapies. In this study, we utilized our previously established fluid shear stress assay to investigate and compare the viscoelastic properties of normal immortalized human astrocytes (IHAs) and invasive human glioblastoma (GBM) cells when subjected to physiological levels of shear stress that are present in the brain microenvironment. We used a parallel-flow microfluidic shear system and a camera-coupled optical microscope to expose single cells to fluid shear stress and monitor the resulting deformation in real-time, respectively. From the video-rate imaging, we fed cell deformation information from digital image correlation into a three-parameter generalized Maxwell model to quantify the nuclear and cytoplasmic viscoelastic properties of single cells. We further quantified actin cytoskeleton density and alignment in IHAs and GBM cells via immunofluorescence microscopy and image analysis techniques. Results from our study show that contrary to the behavior of many extracranial cells, normal and cancerous brain cells do not exhibit significant differences in their viscoelastic behavior. Moreover, we also found that the viscoelastic properties of the nucleus and cytoplasm as well as the actin cytoskeletal densities of both brain cell types are similar. Our work suggests that malignant GBM cells exhibit unique mechanical behaviors not seen in other cancer cell types. These results warrant future study to elucidate the distinct biophysical characteristics of the brain and reveal novel mechanical attributes of GBM and other primary brain tumors. |
format | Online Article Text |
id | pubmed-10557591 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-105575912023-10-07 Single-cell mechanical analysis reveals viscoelastic similarities between normal and neoplastic brain cells Onwudiwe, Killian Najera, Julian Holen, Luke Burchett, Alice A. Rodriguez, Dorielis Zarodniuk, Maksym Siri, Saeed Datta, Meenal bioRxiv Article Understanding cancer cell mechanics allows for the identification of novel disease mechanisms, diagnostic biomarkers, and targeted therapies. In this study, we utilized our previously established fluid shear stress assay to investigate and compare the viscoelastic properties of normal immortalized human astrocytes (IHAs) and invasive human glioblastoma (GBM) cells when subjected to physiological levels of shear stress that are present in the brain microenvironment. We used a parallel-flow microfluidic shear system and a camera-coupled optical microscope to expose single cells to fluid shear stress and monitor the resulting deformation in real-time, respectively. From the video-rate imaging, we fed cell deformation information from digital image correlation into a three-parameter generalized Maxwell model to quantify the nuclear and cytoplasmic viscoelastic properties of single cells. We further quantified actin cytoskeleton density and alignment in IHAs and GBM cells via immunofluorescence microscopy and image analysis techniques. Results from our study show that contrary to the behavior of many extracranial cells, normal and cancerous brain cells do not exhibit significant differences in their viscoelastic behavior. Moreover, we also found that the viscoelastic properties of the nucleus and cytoplasm as well as the actin cytoskeletal densities of both brain cell types are similar. Our work suggests that malignant GBM cells exhibit unique mechanical behaviors not seen in other cancer cell types. These results warrant future study to elucidate the distinct biophysical characteristics of the brain and reveal novel mechanical attributes of GBM and other primary brain tumors. Cold Spring Harbor Laboratory 2023-09-25 /pmc/articles/PMC10557591/ /pubmed/37808779 http://dx.doi.org/10.1101/2023.09.23.559055 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Onwudiwe, Killian Najera, Julian Holen, Luke Burchett, Alice A. Rodriguez, Dorielis Zarodniuk, Maksym Siri, Saeed Datta, Meenal Single-cell mechanical analysis reveals viscoelastic similarities between normal and neoplastic brain cells |
title | Single-cell mechanical analysis reveals viscoelastic similarities between normal and neoplastic brain cells |
title_full | Single-cell mechanical analysis reveals viscoelastic similarities between normal and neoplastic brain cells |
title_fullStr | Single-cell mechanical analysis reveals viscoelastic similarities between normal and neoplastic brain cells |
title_full_unstemmed | Single-cell mechanical analysis reveals viscoelastic similarities between normal and neoplastic brain cells |
title_short | Single-cell mechanical analysis reveals viscoelastic similarities between normal and neoplastic brain cells |
title_sort | single-cell mechanical analysis reveals viscoelastic similarities between normal and neoplastic brain cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557591/ https://www.ncbi.nlm.nih.gov/pubmed/37808779 http://dx.doi.org/10.1101/2023.09.23.559055 |
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