Introduction

The biological and mechanical properties of circulating tumor cells (CTCs) in combination with the hemodynamics affect the preference of metastatic sites in the vasculature. Despite the extensive literature on the effects of biological properties on cell adhesion, the effects of hydrodynamic forces on primary attachment remains an active area of research. Using simulations in conjunction with experimentation, we provide new insight into the interplay of CTCs dynamics and local hydrodynamics.

Methods

A flow experiment of CTC attachment was performed within a bioprinted, double branching endothelialized vessel. Simulations of fluid flow and CTC transport in the reconstructed and idealized bifurcated vessel were respectively performed by HARVEY, our in-house massively parallel computational fluid dynamics solver. HARVEY is based on the lattice Boltzmann and finite element methods to model the fluid and cells dynamics. The immersed boundary method is employed for resolving the fluid–structure interaction.

Results

CTC attachment was quantified experimentally at all regions of the complex vessel. The results demonstrate a clear preference for CTCs to attach at the branch points. To elucidate the effect of the vessel topology on the location of attachment, a fluid-only simulation was performed assessing the differences in the hydrodynamics along the vessel. CTC transport in idealized bifurcated vessels was subsequently studied to examine the effects of cell deformability on the local hydrodynamics patterns and, thus, the preference of attachment sites.

Conclusions

The current work provides evidence on the correlation of the hydrodynamics forces arising from the vessel topology and CTC properties on the attachment regions.

中文翻译：

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通过实验和模拟研究循环肿瘤细胞与局部流体动力学之间的相互作用

介绍

循环肿瘤细胞 (CTC) 的生物学和力学特性与血流动力学相结合会影响脉管系统中转移部位的偏好。尽管有大量关于生物学特性对细胞粘附的影响的文献，但流体动力对初级附着的影响仍然是一个活跃的研究领域。我们将模拟与实验结合使用，为 CTC 动力学和局部流体动力学之间的相互作用提供了新的见解。

方法

在生物打印的双分支内皮血管内进行 CTC 附着的流动实验。我们内部的大规模并行计算流体动力学求解器 HARVEY 分别对重建和理想化的分叉血管中的流体流动和 CTC 传输进行了模拟。HARVEY 基于格子玻尔兹曼和有限元方法来模拟流体和细胞动力学。浸没边界法用于解决流固耦合问题。

结果

在复杂血管的所有区域通过实验对 CTC 附着进行量化。结果表明 CTC 明显倾向于附着在分支点。为了阐明血管拓扑结构对附着位置的影响，进行了仅流体模拟，以评估沿血管的流体动力学差异。随后研究了理想化分叉血管中的 CTC 转运，以检查细胞变形性对局部流体动力学模式的影响，从而影响附着位点的偏好。

结论

目前的工作提供了关于由血管拓扑产生的流体动力与附着区域上的 CTC 特性之间的相关性的证据。