Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments

Abstract Cancer cell metastasis is a major factor in cancer-related mortality. During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. However, the characterization of morphological and subcellular features of cells in s...

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Main Authors: Xingjian Zhang, Trevor Chan, Michael Mak
Format: Article
Language:English
Published: Nature Publishing Group 2021-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-85640-5
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spelling doaj-bace19fc6d1e474c9f19494c6952e9e72021-03-28T11:31:33ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111010.1038/s41598-021-85640-5Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironmentsXingjian Zhang0Trevor Chan1Michael Mak2Department of Biomedical Engineering, Yale UniversityDepartment of Biomedical Engineering, Yale UniversityDepartment of Biomedical Engineering, Yale UniversityAbstract Cancer cell metastasis is a major factor in cancer-related mortality. During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. However, the characterization of morphological and subcellular features of cells in similar migratory phenotypes and the effects of geometric confinement on cell morphodynamics are not well understood. Here, we investigate the phenotypes of highly aggressive MDA-MB-231 cells in single cell and cell doublet (an initial and simplified collective state) forms in confined microenvironments. We group phenotypically similar single cells and cell doublets and characterize related morphological and subcellular features. We further detect two distinct migratory phenotypes, fluctuating and non-fluctuating, within the fast migrating single cell group. In addition, we demonstrate an increase in the number of protrusions formed at the leading edge of cells after invasion through geometric confinement. Finally, we track the short and long term effects of varied degrees of confinement on protrusion formation. Overall, our findings elucidate the underlying morphological and subcellular features associated with different single cell and cell doublet phenotypes and the impact of invasion through confined geometry on cell behavior.https://doi.org/10.1038/s41598-021-85640-5
collection DOAJ
language English
format Article
sources DOAJ
author Xingjian Zhang
Trevor Chan
Michael Mak
spellingShingle Xingjian Zhang
Trevor Chan
Michael Mak
Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments
Scientific Reports
author_facet Xingjian Zhang
Trevor Chan
Michael Mak
author_sort Xingjian Zhang
title Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments
title_short Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments
title_full Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments
title_fullStr Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments
title_full_unstemmed Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments
title_sort morphodynamic signatures of mda-mb-231 single cells and cell doublets undergoing invasion in confined microenvironments
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-03-01
description Abstract Cancer cell metastasis is a major factor in cancer-related mortality. During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. However, the characterization of morphological and subcellular features of cells in similar migratory phenotypes and the effects of geometric confinement on cell morphodynamics are not well understood. Here, we investigate the phenotypes of highly aggressive MDA-MB-231 cells in single cell and cell doublet (an initial and simplified collective state) forms in confined microenvironments. We group phenotypically similar single cells and cell doublets and characterize related morphological and subcellular features. We further detect two distinct migratory phenotypes, fluctuating and non-fluctuating, within the fast migrating single cell group. In addition, we demonstrate an increase in the number of protrusions formed at the leading edge of cells after invasion through geometric confinement. Finally, we track the short and long term effects of varied degrees of confinement on protrusion formation. Overall, our findings elucidate the underlying morphological and subcellular features associated with different single cell and cell doublet phenotypes and the impact of invasion through confined geometry on cell behavior.
url https://doi.org/10.1038/s41598-021-85640-5
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AT trevorchan morphodynamicsignaturesofmdamb231singlecellsandcelldoubletsundergoinginvasioninconfinedmicroenvironments
AT michaelmak morphodynamicsignaturesofmdamb231singlecellsandcelldoubletsundergoinginvasioninconfinedmicroenvironments
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