Single-cell adhesion strength and contact density drops in the M phase of cancer cells

Abstract The high throughput, cost effective and sensitive quantification of cell adhesion strength at the single-cell level is still a challenging task. The adhesion force between tissue cells and their environment is crucial in all multicellular organisms. Integrins transmit force between the intr...

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Autores principales: Rita Ungai-Salánki, Eleonóra Haty, Tamás Gerecsei, Barbara Francz, Bálint Béres, Milán Sztilkovics, Inna Székács, Bálint Szabó, Robert Horvath
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:1e57f26a531f443cbb4f3def0a0203292021-12-02T18:50:03ZSingle-cell adhesion strength and contact density drops in the M phase of cancer cells10.1038/s41598-021-97734-12045-2322https://doaj.org/article/1e57f26a531f443cbb4f3def0a0203292021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97734-1https://doaj.org/toc/2045-2322Abstract The high throughput, cost effective and sensitive quantification of cell adhesion strength at the single-cell level is still a challenging task. The adhesion force between tissue cells and their environment is crucial in all multicellular organisms. Integrins transmit force between the intracellular cytoskeleton and the extracellular matrix. This force is not only a mechanical interaction but a way of signal transduction as well. For instance, adhesion-dependent cells switch to an apoptotic mode in the lack of adhesion forces. Adhesion of tumor cells is a potential therapeutic target, as it is actively modulated during tissue invasion and cell release to the bloodstream resulting in metastasis. We investigated the integrin-mediated adhesion between cancer cells and their RGD (Arg-Gly-Asp) motif displaying biomimetic substratum using the HeLa cell line transfected by the Fucci fluorescent cell cycle reporter construct. We employed a computer-controlled micropipette and a high spatial resolution label-free resonant waveguide grating-based optical sensor calibrated to adhesion force and energy at the single-cell level. We found that the overall adhesion strength of single cancer cells is approximately constant in all phases except the mitotic (M) phase with a significantly lower adhesion. Single-cell evanescent field based biosensor measurements revealed that at the mitotic phase the cell material mass per unit area inside the cell-substratum contact zone is significantly less, too. Importantly, the weaker mitotic adhesion is not simply a direct consequence of the measured smaller contact area. Our results highlight these differences in the mitotic reticular adhesions and confirm that cell adhesion is a promising target of selective cancer drugs as the vast majority of normal, differentiated tissue cells do not enter the M phase and do not divide.Rita Ungai-SalánkiEleonóra HatyTamás GerecseiBarbara FranczBálint BéresMilán SztilkovicsInna SzékácsBálint SzabóRobert HorvathNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Rita Ungai-Salánki
Eleonóra Haty
Tamás Gerecsei
Barbara Francz
Bálint Béres
Milán Sztilkovics
Inna Székács
Bálint Szabó
Robert Horvath
Single-cell adhesion strength and contact density drops in the M phase of cancer cells
description Abstract The high throughput, cost effective and sensitive quantification of cell adhesion strength at the single-cell level is still a challenging task. The adhesion force between tissue cells and their environment is crucial in all multicellular organisms. Integrins transmit force between the intracellular cytoskeleton and the extracellular matrix. This force is not only a mechanical interaction but a way of signal transduction as well. For instance, adhesion-dependent cells switch to an apoptotic mode in the lack of adhesion forces. Adhesion of tumor cells is a potential therapeutic target, as it is actively modulated during tissue invasion and cell release to the bloodstream resulting in metastasis. We investigated the integrin-mediated adhesion between cancer cells and their RGD (Arg-Gly-Asp) motif displaying biomimetic substratum using the HeLa cell line transfected by the Fucci fluorescent cell cycle reporter construct. We employed a computer-controlled micropipette and a high spatial resolution label-free resonant waveguide grating-based optical sensor calibrated to adhesion force and energy at the single-cell level. We found that the overall adhesion strength of single cancer cells is approximately constant in all phases except the mitotic (M) phase with a significantly lower adhesion. Single-cell evanescent field based biosensor measurements revealed that at the mitotic phase the cell material mass per unit area inside the cell-substratum contact zone is significantly less, too. Importantly, the weaker mitotic adhesion is not simply a direct consequence of the measured smaller contact area. Our results highlight these differences in the mitotic reticular adhesions and confirm that cell adhesion is a promising target of selective cancer drugs as the vast majority of normal, differentiated tissue cells do not enter the M phase and do not divide.
format article
author Rita Ungai-Salánki
Eleonóra Haty
Tamás Gerecsei
Barbara Francz
Bálint Béres
Milán Sztilkovics
Inna Székács
Bálint Szabó
Robert Horvath
author_facet Rita Ungai-Salánki
Eleonóra Haty
Tamás Gerecsei
Barbara Francz
Bálint Béres
Milán Sztilkovics
Inna Székács
Bálint Szabó
Robert Horvath
author_sort Rita Ungai-Salánki
title Single-cell adhesion strength and contact density drops in the M phase of cancer cells
title_short Single-cell adhesion strength and contact density drops in the M phase of cancer cells
title_full Single-cell adhesion strength and contact density drops in the M phase of cancer cells
title_fullStr Single-cell adhesion strength and contact density drops in the M phase of cancer cells
title_full_unstemmed Single-cell adhesion strength and contact density drops in the M phase of cancer cells
title_sort single-cell adhesion strength and contact density drops in the m phase of cancer cells
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/1e57f26a531f443cbb4f3def0a020329
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