表型转换机制决定了 "要么走要么长 "假说下细胞向细胞外基质迁移的结构

Rebecca M. Crossley, Kevin J. Painter, Tommaso Lorenzi, Philip K. Maini, Ruth E. Baker
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引用次数: 0

摘要

虽然目前的数学模型经常考虑细胞群的离散表型结构,与 "要么走要么长 "的假说一致,但它们经常忽视环境在决定细胞迁移过程中的表型方面可能发挥的作用。本研究比较了以前研究过的由能增殖、移动和降解细胞外基质(ECM)的通用细胞组成的均质群体的体积填充模型(cite{crossley2023travelling})和由能移动和降解ECM或增殖的两个不同的专业细胞亚群组成的异质群体的新型模型,探讨了不同的假定表型转换机制如何影响入侵细胞群体的速度和结构。通过从基于个体的模型衍生出的连续模型,我们可以深入了解 ECM 的影响以及表型转换对迁移细胞群的影响。值得注意的是,与普通细胞群相比,不能切换表型的专性细胞群显示出较低的侵袭性,而实施不同形式的切换会显著改变迁移细胞前沿的结构。这一关键结果表明,入侵细胞群的结构可用来推断表型转换的基本机制。
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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 \cite{hatzikirou2012go, stepien2018traveling}, 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) \cite{crossley2023travelling} 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.
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