Cell-scale biophysical determinants of cell competition in epithelia
How cells with different genetic makeups compete in tissues is an outstanding question in developmental biology and cancer research. Studies in recent years have revealed that cell competition can either be driven by short-range biochemical signalling or by long-range mechanical stresses in the tiss...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/61011 |
| _version_ | 1811180632315789312 |
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| author | Daniel Gradeci Anna Bove Giulia Vallardi Alan R Lowe Shiladitya Banerjee Guillaume Charras |
| author_facet | Daniel Gradeci Anna Bove Giulia Vallardi Alan R Lowe Shiladitya Banerjee Guillaume Charras |
| author_sort | Daniel Gradeci |
| collection | DOAJ |
| description | How cells with different genetic makeups compete in tissues is an outstanding question in developmental biology and cancer research. Studies in recent years have revealed that cell competition can either be driven by short-range biochemical signalling or by long-range mechanical stresses in the tissue. To date, cell competition has generally been characterised at the population scale, leaving the single-cell-level mechanisms of competition elusive. Here, we use high time-resolution experimental data to construct a multi-scale agent-based model for epithelial cell competition and use it to gain a conceptual understanding of the cellular factors that governs competition in cell populations within tissues. We find that a key determinant of mechanical competition is the difference in homeostatic density between winners and losers, while differences in growth rates and tissue organisation do not affect competition end result. In contrast, the outcome and kinetics of biochemical competition is strongly influenced by local tissue organisation. Indeed, when loser cells are homogenously mixed with winners at the onset of competition, they are eradicated; however, when they are spatially separated, winner and loser cells coexist for long times. These findings suggest distinct biophysical origins for mechanical and biochemical modes of cell competition. |
| first_indexed | 2024-04-11T09:06:26Z |
| format | Article |
| id | doaj.art-a7eb59c480d64f3284720e2100b5d57a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:06:26Z |
| publishDate | 2021-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a7eb59c480d64f3284720e2100b5d57a2022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2021-05-011010.7554/eLife.61011Cell-scale biophysical determinants of cell competition in epitheliaDaniel Gradeci0Anna Bove1Giulia Vallardi2Alan R Lowe3https://orcid.org/0000-0002-0558-3597Shiladitya Banerjee4https://orcid.org/0000-0001-8000-2556Guillaume Charras5https://orcid.org/0000-0002-7902-0279Department of Physics and Astronomy, University College London, London, United Kingdom; London Centre for Nanotechnology, University College London, London, United KingdomLondon Centre for Nanotechnology, University College London, London, United Kingdom; Department of Cell and Developmental Biology, University College London, London, United KingdomInstitute for Structural and Molecular Biology, University College London, London, United KingdomLondon Centre for Nanotechnology, University College London, London, United Kingdom; Institute for Structural and Molecular Biology, University College London, London, United Kingdom; Institute for the Physics of Living Systems, University College London, London, United KingdomDepartment of Physics and Astronomy, University College London, London, United Kingdom; Institute for the Physics of Living Systems, University College London, London, United Kingdom; Department of Physics, Carnegie Mellon University, Pittsburgh, United StatesLondon Centre for Nanotechnology, University College London, London, United Kingdom; Department of Cell and Developmental Biology, University College London, London, United Kingdom; Institute for the Physics of Living Systems, University College London, London, United KingdomHow cells with different genetic makeups compete in tissues is an outstanding question in developmental biology and cancer research. Studies in recent years have revealed that cell competition can either be driven by short-range biochemical signalling or by long-range mechanical stresses in the tissue. To date, cell competition has generally been characterised at the population scale, leaving the single-cell-level mechanisms of competition elusive. Here, we use high time-resolution experimental data to construct a multi-scale agent-based model for epithelial cell competition and use it to gain a conceptual understanding of the cellular factors that governs competition in cell populations within tissues. We find that a key determinant of mechanical competition is the difference in homeostatic density between winners and losers, while differences in growth rates and tissue organisation do not affect competition end result. In contrast, the outcome and kinetics of biochemical competition is strongly influenced by local tissue organisation. Indeed, when loser cells are homogenously mixed with winners at the onset of competition, they are eradicated; however, when they are spatially separated, winner and loser cells coexist for long times. These findings suggest distinct biophysical origins for mechanical and biochemical modes of cell competition.https://elifesciences.org/articles/61011cell competitionMDCKbiophysicssimulation |
| spellingShingle | Daniel Gradeci Anna Bove Giulia Vallardi Alan R Lowe Shiladitya Banerjee Guillaume Charras Cell-scale biophysical determinants of cell competition in epithelia eLife cell competition MDCK biophysics simulation |
| title | Cell-scale biophysical determinants of cell competition in epithelia |
| title_full | Cell-scale biophysical determinants of cell competition in epithelia |
| title_fullStr | Cell-scale biophysical determinants of cell competition in epithelia |
| title_full_unstemmed | Cell-scale biophysical determinants of cell competition in epithelia |
| title_short | Cell-scale biophysical determinants of cell competition in epithelia |
| title_sort | cell scale biophysical determinants of cell competition in epithelia |
| topic | cell competition MDCK biophysics simulation |
| url | https://elifesciences.org/articles/61011 |
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