Wijeratne Peter A, Hipwell John H, Hawkes David J, Stylianopoulos Triantafyllos, Vavourakis Vasileios
Department of Computer Science, University College London, London, United Kingdom.
Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom.
PLoS One. 2017 Sep 13;12(9):e0184511. doi: 10.1371/journal.pone.0184511. eCollection 2017.
We present an in-silico model of avascular poroelastic tumour growth coupled with a multiscale biphasic description of the tumour-host environment. The model is specified to in-vitro data, facilitating biophysically realistic simulations of tumour spheroid growth into a dense collagen hydrogel. We use the model to first confirm that passive mechanical remodelling of collagen fibres at the tumour boundary is driven by solid stress, and not fluid pressure. The model is then used to demonstrate the influence of collagen microstructure on peritumoural permeability and interstitial fluid flow. Our model suggests that at the tumour periphery, remodelling causes the peritumoural stroma to become more permeable in the circumferential than radial direction, and the interstitial fluid velocity is found to be dependent on initial collagen alignment. Finally we show that solid stresses are negatively correlated with peritumoural permeability, and positively correlated with interstitial fluid velocity. These results point to a heterogeneous, microstructure-dependent force environment at the tumour-peritumoural stroma interface.
我们提出了一种无血管多孔弹性肿瘤生长的计算机模拟模型，并结合了肿瘤-宿主环境的多尺度双相描述。该模型根据体外数据进行了设定，有助于对肿瘤球体在致密胶原水凝胶中的生长进行生物物理逼真的模拟。我们首先使用该模型确认肿瘤边界处胶原纤维的被动机械重塑是由固体应力驱动的，而非流体压力。然后，该模型用于证明胶原微观结构对肿瘤周围渗透性和间质液流动的影响。我们的模型表明，在肿瘤周边，重塑使肿瘤周围基质在圆周方向上比径向方向上更具渗透性，并且发现间质液速度取决于初始胶原排列。最后，我们表明固体应力与肿瘤周围渗透性呈负相关，与间质液速度呈正相关。这些结果表明在肿瘤-肿瘤周围基质界面存在异质性的、依赖于微观结构的力环境。
