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肿瘤球体中表面张力驱动的边界生长。

Surface tension-driven boundary growth in tumour spheroids.

作者信息

Riccobelli Davide

机构信息

mathLab - Mathematics Area, SISSA, Trieste, Italy.

MOX - Dipartimento di Matematica, Politecnico di Milano, Milano, Italy.

出版信息

Interface Focus. 2025 May 16;15(2):20240035. doi: 10.1098/rsfs.2024.0035.

Abstract

Growing experimental evidence highlights the relevant role of mechanics in the physiology of solid tumours, even in their early stages. While most of the mathematical models describe tumour growth as a volumetric increase in mass in the bulk, experiments on tumour spheroids have demonstrated that cell proliferation occurs in a thin layer at the boundary of the cellular aggregate. In this work, we investigate how elasticity and surface tension interact during the development of tumour spheroids. We model the spheroid as a hyperelastic material undergoing boundary accretion, where the newly created cells are deformed by the action of surface tension. This growth leads to a frustrated reference configuration, resulting in the appearance of residual stress. Our theoretical framework is validated using experimental results from the literature. Like fully developed tumours, spheroids open when subjected to radial cuts. Remarkably, this behaviour is observed even in newly formed spheroids, which lack residual stress. Through both analytical solutions and numerical simulations, we show that this phenomenon is driven by elastocapillary interactions, where the residual stress developed in grown spheroids amplifies the tumour opening. Our model's outcomes align with experimental observations and allow us to estimate the surface tension acting on tumour spheroids.

摘要

越来越多的实验证据突出了力学在实体瘤生理学中的相关作用,即使在其早期阶段也是如此。虽然大多数数学模型将肿瘤生长描述为整体质量的体积增加,但对肿瘤球体的实验表明,细胞增殖发生在细胞聚集体边界的薄层中。在这项工作中,我们研究了肿瘤球体发育过程中弹性和表面张力是如何相互作用的。我们将球体建模为一种经历边界增生的超弹性材料,新产生的细胞在表面张力的作用下发生变形。这种生长导致了一个受阻的参考构型,从而产生残余应力。我们的理论框架通过文献中的实验结果得到了验证。与完全发育的肿瘤一样,球体在受到径向切割时会张开。值得注意的是,即使在缺乏残余应力的新形成的球体中也观察到了这种行为。通过解析解和数值模拟,我们表明这种现象是由弹性毛细管相互作用驱动的,其中在生长的球体中产生的残余应力会放大肿瘤的张开。我们模型的结果与实验观察结果一致,并使我们能够估计作用在肿瘤球体上的表面张力。

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