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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-97734-1 |
| _version_ | 1818718895901507584 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T19:58:19Z |
| format | Article |
| id | doaj.art-1e57f26a531f443cbb4f3def0a020329 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T19:58:19Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1e57f26a531f443cbb4f3def0a0203292022-12-21T21:34:32ZengNature PortfolioScientific Reports2045-23222021-09-0111111310.1038/s41598-021-97734-1Single-cell adhesion strength and contact density drops in the M phase of cancer cellsRita Ungai-Salánki0Eleonóra Haty1Tamás Gerecsei2Barbara Francz3Bálint Béres4Milán Sztilkovics5Inna Székács6Bálint Szabó7Robert Horvath8Department of Biological Physics, ELTE Eötvös Loránd UniversityNanobiosensorics Laboratory, ELKH, Institute for Technical Physics and Materials Science, Centre for Energy ResearchDepartment of Biological Physics, ELTE Eötvös Loránd UniversityCellSorter Scientific Company for InnovationsNanobiosensorics Laboratory, ELKH, Institute for Technical Physics and Materials Science, Centre for Energy ResearchNanobiosensorics Laboratory, ELKH, Institute for Technical Physics and Materials Science, Centre for Energy ResearchNanobiosensorics Laboratory, ELKH, Institute for Technical Physics and Materials Science, Centre for Energy ResearchDepartment of Biological Physics, ELTE Eötvös Loránd UniversityNanobiosensorics Laboratory, ELKH, Institute for Technical Physics and Materials Science, Centre for Energy ResearchAbstract 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.https://doi.org/10.1038/s41598-021-97734-1 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-97734-1 |
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