3D hybrid modelling of vascular network formation
3D hybrid modelling of vascular network formation
复制标题
DOI：
10.1016/j.jtbi.2016.11.013
复制
发表时间：
2017-02-07
影响因子：
2
通讯作者：
Byrne, Helen M.
中科院分区：
文献类型：
--
作者：
Perfahl, Holger;Hughes, Barry D.;Byrne, Helen M.
我们开发了一个非晶格的、基于试剂的模型来描述血管生成，即血管内皮祖细胞在发育过程中的从头形成。构成我们血管网络的内皮细胞被视为线性弹性球体，随着它们所受的力而运动。我们区分了两种类型的内皮细胞：血管分子包含在网络中，尖端细胞位于血管的末端。尖端细胞的移动响应于与邻近血管元素和局部组织环境相互作用所产生的机械力、趋化力和持续力，这是它们倾向于继续向同一方向移动的原因。导管分子受到类似的机械力，但对趋化性不敏感。引入一个代表与局部组织相互作用的角持续力来稳定由细胞增殖引起的屈曲不稳定性。只有血管分子的增殖速度取决于它们的拉伸程度：拉长的分子增加了增殖的速度，压缩的分子降低了增殖的速度。分裂后，新细胞的命运取决于局部机械环境：如果母体血管高度压缩，形成新芽的可能性增加，如果母体血管被拉伸，则被并入母体血管的可能性增加。模拟结果表明，我们的混合模型可以重现血管生成的关键质量特征。广泛的参数敏感性分析表明，改变TIP细胞的趋化敏感性，以及增殖率和发芽概率对机械拉伸的敏感性，可以引起网络大小和形态的显著变化。改变趋化敏感性直接影响网络的方向性。分支的程度以及网络的密度受萌发概率的影响。引入了同时描述几个网络属性的字形，以显示这些和其他网络量如何随时间以及模型参数的变化而变化。我们还展示了从活体数据构建的等效字形如何用于区分正常和肿瘤血管系统，并从长远来看，用于模型验证。我们的结论是，我们的生物力学混合模型可以产生与体外和体内实验产生的血管网络定性相似的血管网络。
We develop an off-lattice, agent-based model to describe vasculogenesis, the de novo formation of blood vessels from endothelial progenitor cells during development. The endothelial cells that comprise our vessel network are viewed as linearly elastic spheres that move in response to the forces they experience. We distinguish two types of endothelial cells: vessel elements are contained within the network and tip cells are located at the ends of vessels. Tip cells move in response to mechanical forces caused by interactions with neighbouring vessel elements and the local tissue environment, chemotactic forces and a persistence force which accounts for their tendency to continue moving in the same direction. Vessel elements are subject to similar mechanical forces but are insensitive to chemotaxis. An angular persistence force representing interactions with the local tissue is introduced to stabilise buckling instabilities caused by cell proliferation. Only vessel elements proliferate, at rates which depend on their degree of stretch: elongated elements have increased rates of proliferation, and compressed elements have reduced rates. Following division, the fate of the new cell depends on the local mechanical environment: the probability of forming a new sprout is increased if the parent vessel is highly compressed and the probability of being incorporated into the parent vessel increased if the parent is stretched. Simulation results reveal that our hybrid model can reproduce the key qualitative features-of vasculogenesis. Extensive parameter sensitivity analyses show that significant changes in network size and morphology are induced by varying the chemotactic sensitivity of tip cells, and the sensitivities of the proliferation rate and the sprouting probability to mechanical stretch. Varying the chemotactic sensitivity directly influences the directionality of the networks. The degree of branching, and thereby the density of the networks, is influenced by the sprouting probability. Glyphs that simultaneously depict several network properties are introduced to show how these and other network quantities change over time and also as model parameters vary. We also show how equivalent glyphs constructed from in vivo data could be used to discriminate between normal and tumour vasculature and, in the longer term, for model validation. We conclude that our biomechanical hybrid model can generate vascular networks that are qualitatively similar to those generated from in vitro and in vivo experiments.