Phenotypic switching mechanisms determine the structure of cell migration into extracellular matrix under the ‘go-or-grow’ hypothesis
A fundamental feature of collective cell migration is phenotypic heterogeneity which, for example, influences tumour progression and relapse. While current mathematical models often consider discrete phenotypic structuring of the cell population, in-line with the ‘go-or-grow’ hypothesis [1, 2], they...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2024
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| _version_ | 1811140591004680192 |
|---|---|
| author | Crossley, R Painter, K Lorenzi, T Maini, P Baker, R |
| author_facet | Crossley, R Painter, K Lorenzi, T Maini, P Baker, R |
| author_sort | Crossley, R |
| collection | OXFORD |
| description | A fundamental feature of collective cell migration is phenotypic heterogeneity which, for example, influences tumour
progression and relapse. While current mathematical models often consider discrete phenotypic structuring of the
cell population, in-line with the ‘go-or-grow’ hypothesis [1, 2], they regularly overlook the role that the environment
may play in determining the cells’ phenotype during migration. Comparing a previously studied volume-filling
model for a homogeneous population of generalist cells that can proliferate, move and degrade extracellular matrix
(ECM) [3] to a novel model for a heterogeneous population comprising two distinct sub-populations of specialist
cells that can either move and degrade ECM or proliferate, this study explores how different hypothetical phenotypic
switching mechanisms affect the speed and structure of the invading cell populations. Through a continuum model
derived from its individual-based counterpart, insights into the influence of the ECM and the impact of phenotypic
switching on migrating cell populations emerge. Notably, specialist cell populations that cannot switch phenotype
show reduced invasiveness compared to generalist cell populations, while implementing different forms of switching
significantly alters the structure of migrating cell fronts. This key result suggests that the structure of an invading
cell population could be used to infer the underlying mechanisms governing phenotypic switching |
| first_indexed | 2024-09-25T04:24:25Z |
| format | Journal article |
| id | oxford-uuid:0285bbc6-06a6-4662-bef2-e160385e1d59 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:24:25Z |
| publishDate | 2024 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:0285bbc6-06a6-4662-bef2-e160385e1d592024-08-22T11:45:22ZPhenotypic switching mechanisms determine the structure of cell migration into extracellular matrix under the ‘go-or-grow’ hypothesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0285bbc6-06a6-4662-bef2-e160385e1d59EnglishSymplectic ElementsElsevier2024Crossley, RPainter, KLorenzi, TMaini, PBaker, RA fundamental feature of collective cell migration is phenotypic heterogeneity which, for example, influences tumour progression and relapse. While current mathematical models often consider discrete phenotypic structuring of the cell population, in-line with the ‘go-or-grow’ hypothesis [1, 2], they regularly overlook the role that the environment may play in determining the cells’ phenotype during migration. Comparing a previously studied volume-filling model for a homogeneous population of generalist cells that can proliferate, move and degrade extracellular matrix (ECM) [3] to a novel model for a heterogeneous population comprising two distinct sub-populations of specialist cells that can either move and degrade ECM or proliferate, this study explores how different hypothetical phenotypic switching mechanisms affect the speed and structure of the invading cell populations. Through a continuum model derived from its individual-based counterpart, insights into the influence of the ECM and the impact of phenotypic switching on migrating cell populations emerge. Notably, specialist cell populations that cannot switch phenotype show reduced invasiveness compared to generalist cell populations, while implementing different forms of switching significantly alters the structure of migrating cell fronts. This key result suggests that the structure of an invading cell population could be used to infer the underlying mechanisms governing phenotypic switching |
| spellingShingle | Crossley, R Painter, K Lorenzi, T Maini, P Baker, R Phenotypic switching mechanisms determine the structure of cell migration into extracellular matrix under the ‘go-or-grow’ hypothesis |
| title | Phenotypic switching mechanisms determine the structure of cell migration into extracellular matrix under the ‘go-or-grow’ hypothesis |
| title_full | Phenotypic switching mechanisms determine the structure of cell migration into extracellular matrix under the ‘go-or-grow’ hypothesis |
| title_fullStr | Phenotypic switching mechanisms determine the structure of cell migration into extracellular matrix under the ‘go-or-grow’ hypothesis |
| title_full_unstemmed | Phenotypic switching mechanisms determine the structure of cell migration into extracellular matrix under the ‘go-or-grow’ hypothesis |
| title_short | Phenotypic switching mechanisms determine the structure of cell migration into extracellular matrix under the ‘go-or-grow’ hypothesis |
| title_sort | phenotypic switching mechanisms determine the structure of cell migration into extracellular matrix under the go or grow hypothesis |
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