Age structure can account for delayed logistic proliferation of scratch assays

Scratch assays are in vitro methods for studying cell migration. In these experiments, a scratch is made on a cell monolayer and recolonisation of the scratched region is imaged to quantify cell migration rates. Typically, scratch assays are modelled by reaction diffusion equations depicting cell mi...

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Príomhchruthaitheoirí: Ponce Bobadilla, AV, Carraro, T, Byrne, HM, Maini, PK, Alarcón, T
Formáid: Journal article
Teanga:English
Foilsithe / Cruthaithe: Springer 2019
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author Ponce Bobadilla, AV
Carraro, T
Byrne, HM
Maini, PK
Alarcón, T
author_facet Ponce Bobadilla, AV
Carraro, T
Byrne, HM
Maini, PK
Alarcón, T
author_sort Ponce Bobadilla, AV
collection OXFORD
description Scratch assays are in vitro methods for studying cell migration. In these experiments, a scratch is made on a cell monolayer and recolonisation of the scratched region is imaged to quantify cell migration rates. Typically, scratch assays are modelled by reaction diffusion equations depicting cell migration by Fickian diffusion and proliferation by a logistic term. In a recent paper (Jin et al. in Bull Math Biol 79(5):1028–1050, 2017), the authors observed experimentally that during the early stage of the recolonisation process, there is a disturbance phase where proliferation is not logistic, and this is followed by a growth phase where proliferation appears to be logistic. The authors did not identify the precise mechanism that causes the disturbance phase but showed that ignoring it can lead to incorrect parameter estimates. The aim of this work is to show that a nonlinear age-structured population model can account for the two phases of proliferation in scratch assays. The model consists of an age-structured cell cycle model of a cell population, coupled with an ordinary differential equation describing the resource concentration dynamics in the substrate. The model assumes a resource-dependent cell cycle threshold age, above which cells are able to proliferate. By studying the dynamics of the full system in terms of the subpopulations of cells that can proliferate and the ones that can not, we are able to find conditions under which the model captures the two-phase behaviour. Through numerical simulations, we are able to show that the interplay between the resource concentration in the substrate and the cell subpopulations dynamics can explain the biphasic dynamics.
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spelling oxford-uuid:b6901d67-9cfc-4415-868e-3a07ba89898b2022-03-27T04:41:53ZAge structure can account for delayed logistic proliferation of scratch assaysJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b6901d67-9cfc-4415-868e-3a07ba89898bEnglishSymplectic Elements at OxfordSpringer2019Ponce Bobadilla, AVCarraro, TByrne, HMMaini, PKAlarcón, TScratch assays are in vitro methods for studying cell migration. In these experiments, a scratch is made on a cell monolayer and recolonisation of the scratched region is imaged to quantify cell migration rates. Typically, scratch assays are modelled by reaction diffusion equations depicting cell migration by Fickian diffusion and proliferation by a logistic term. In a recent paper (Jin et al. in Bull Math Biol 79(5):1028–1050, 2017), the authors observed experimentally that during the early stage of the recolonisation process, there is a disturbance phase where proliferation is not logistic, and this is followed by a growth phase where proliferation appears to be logistic. The authors did not identify the precise mechanism that causes the disturbance phase but showed that ignoring it can lead to incorrect parameter estimates. The aim of this work is to show that a nonlinear age-structured population model can account for the two phases of proliferation in scratch assays. The model consists of an age-structured cell cycle model of a cell population, coupled with an ordinary differential equation describing the resource concentration dynamics in the substrate. The model assumes a resource-dependent cell cycle threshold age, above which cells are able to proliferate. By studying the dynamics of the full system in terms of the subpopulations of cells that can proliferate and the ones that can not, we are able to find conditions under which the model captures the two-phase behaviour. Through numerical simulations, we are able to show that the interplay between the resource concentration in the substrate and the cell subpopulations dynamics can explain the biphasic dynamics.
spellingShingle Ponce Bobadilla, AV
Carraro, T
Byrne, HM
Maini, PK
Alarcón, T
Age structure can account for delayed logistic proliferation of scratch assays
title Age structure can account for delayed logistic proliferation of scratch assays
title_full Age structure can account for delayed logistic proliferation of scratch assays
title_fullStr Age structure can account for delayed logistic proliferation of scratch assays
title_full_unstemmed Age structure can account for delayed logistic proliferation of scratch assays
title_short Age structure can account for delayed logistic proliferation of scratch assays
title_sort age structure can account for delayed logistic proliferation of scratch assays
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