论文标题
使用趋化性驱动的多相模型形成血管状结构
Formation of vascular-like structures using a chemotaxis-driven multiphase model
论文作者
论文摘要
我们提出了一个基于多相模型框架的模式形成的连续模型,以探索细胞外基质内的体外细胞模式。我们证明,在此框架内,趋化驱动的细胞迁移可以分别导致细胞簇和1D和2D中的血管状结构的形成。还研究了对多相组织模型中通常包含的其他机制的模式形成的影响,包括细胞 - 基质牵引,接触抑制和细胞 - 细胞聚集。使用灵敏度分析,评估每个模型参数对仿真结果的相对影响以识别所涉及的关键参数。在先前的实验研究中,进一步包括了化学吸引剂 - 矩阵结合,并将图案的空间尺度扩大到生物学上合理的范围内。证明了有或没有趋化剂 - 矩阵结合的1D模型的深入参数分析的关键发现,可以很好地转化为2D模型,从而获得多个参数状态的血管样细胞模式。总体而言,我们展示了一种生物学动机的多相模型,该模型能够在1D和2D中以生物学上合理的空间尺度产生长期模式形成,并应用用于对体外血管网络形成进行建模。
We propose a continuum model for pattern formation, based on the multiphase model framework, to explore in vitro cell patterning within an extracellular matrix. We demonstrate that, within this framework, chemotaxis-driven cell migration can lead to formation of cell clusters and vascular-like structures in 1D and 2D respectively. The influence on pattern formation of additional mechanisms commonly included in multiphase tissue models, including cell-matrix traction, contact inhibition, and cell-cell aggregation, are also investigated. Using sensitivity analysis, the relative impact of each model parameter on the simulation outcomes is assessed to identify the key parameters involved. Chemoattractant-matrix binding is further included, motivated by previous experimental studies, and to augment the spatial scale of patterning to within a biologically plausible range. Key findings from the in-depth parameter analysis of the 1D models, both with and without chemoattractant-matrix binding, are demonstrated to translate well to the 2D model, obtaining vascular-like cell patterning for multiple parameter regimes. Overall, we demonstrate a biologically-motivated multiphase model capable of generating long-term pattern formation on a biologically plausible spatial scale both in 1D and 2D, with applications for modelling in vitro vascular network formation.