Physical Biomarkers of Disease Progression: On-Chip Monitoring of Changes in Mechanobiology of Colorectal Cancer Cells

Abstract Disease can induce changes to subcellular components, altering cell phenotype and leading to measurable bulk-material mechanical properties. The mechanical phenotyping of single cells therefore offers many potential diagnostic applications. Cells are viscoelastic and their response to an ap...

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Autores principales:	Fern J. Armistead, Julia Gala De Pablo, Hermes Gadêlha, Sally A. Peyman, Stephen D. Evans
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0d0ab460529942fabce44e17105ff0b2
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spelling	oai:doaj.org-article:0d0ab460529942fabce44e17105ff0b22021-12-02T16:23:09ZPhysical Biomarkers of Disease Progression: On-Chip Monitoring of Changes in Mechanobiology of Colorectal Cancer Cells10.1038/s41598-020-59952-x2045-2322https://doaj.org/article/0d0ab460529942fabce44e17105ff0b22020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-59952-xhttps://doaj.org/toc/2045-2322Abstract Disease can induce changes to subcellular components, altering cell phenotype and leading to measurable bulk-material mechanical properties. The mechanical phenotyping of single cells therefore offers many potential diagnostic applications. Cells are viscoelastic and their response to an applied stress is highly dependent on the magnitude and timescale of the actuation. Microfluidics can be used to measure cell deformability over a wide range of flow conditions, operating two distinct flow regimes (shear and inertial) which can expose subtle mechanical properties arising from subcellular components. Here, we investigate the deformability of three colorectal cancer (CRC) cell lines using a range of flow conditions. These cell lines offer a model for CRC metastatic progression; SW480 derived from primary adenocarcinoma, HT29 from a more advanced primary tumor and SW620 from lymph-node metastasis. HL60 (leukemia cells) were also studied as a model circulatory cell, offering a non-epithelial comparison. We demonstrate that microfluidic induced flow deformation can be used to robustly detect mechanical changes associated with CRC progression. We also show that single-cell multivariate analysis, utilising deformation and relaxation dynamics, offers potential to distinguish these different cell types. These results point to the benefit of multiparameter determination for improving detection and accuracy of disease stage diagnosis.Fern J. ArmisteadJulia Gala De PabloHermes GadêlhaSally A. PeymanStephen D. EvansNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fern J. Armistead Julia Gala De Pablo Hermes Gadêlha Sally A. Peyman Stephen D. Evans Physical Biomarkers of Disease Progression: On-Chip Monitoring of Changes in Mechanobiology of Colorectal Cancer Cells
description	Abstract Disease can induce changes to subcellular components, altering cell phenotype and leading to measurable bulk-material mechanical properties. The mechanical phenotyping of single cells therefore offers many potential diagnostic applications. Cells are viscoelastic and their response to an applied stress is highly dependent on the magnitude and timescale of the actuation. Microfluidics can be used to measure cell deformability over a wide range of flow conditions, operating two distinct flow regimes (shear and inertial) which can expose subtle mechanical properties arising from subcellular components. Here, we investigate the deformability of three colorectal cancer (CRC) cell lines using a range of flow conditions. These cell lines offer a model for CRC metastatic progression; SW480 derived from primary adenocarcinoma, HT29 from a more advanced primary tumor and SW620 from lymph-node metastasis. HL60 (leukemia cells) were also studied as a model circulatory cell, offering a non-epithelial comparison. We demonstrate that microfluidic induced flow deformation can be used to robustly detect mechanical changes associated with CRC progression. We also show that single-cell multivariate analysis, utilising deformation and relaxation dynamics, offers potential to distinguish these different cell types. These results point to the benefit of multiparameter determination for improving detection and accuracy of disease stage diagnosis.
format	article
author	Fern J. Armistead Julia Gala De Pablo Hermes Gadêlha Sally A. Peyman Stephen D. Evans
author_facet	Fern J. Armistead Julia Gala De Pablo Hermes Gadêlha Sally A. Peyman Stephen D. Evans
author_sort	Fern J. Armistead
title	Physical Biomarkers of Disease Progression: On-Chip Monitoring of Changes in Mechanobiology of Colorectal Cancer Cells
title_short	Physical Biomarkers of Disease Progression: On-Chip Monitoring of Changes in Mechanobiology of Colorectal Cancer Cells
title_full	Physical Biomarkers of Disease Progression: On-Chip Monitoring of Changes in Mechanobiology of Colorectal Cancer Cells
title_fullStr	Physical Biomarkers of Disease Progression: On-Chip Monitoring of Changes in Mechanobiology of Colorectal Cancer Cells
title_full_unstemmed	Physical Biomarkers of Disease Progression: On-Chip Monitoring of Changes in Mechanobiology of Colorectal Cancer Cells
title_sort	physical biomarkers of disease progression: on-chip monitoring of changes in mechanobiology of colorectal cancer cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/0d0ab460529942fabce44e17105ff0b2
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Physical Biomarkers of Disease Progression: On-Chip Monitoring of Changes in Mechanobiology of Colorectal Cancer Cells

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