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Investigating the Interaction Between Circulating Tumor Cells and Local Hydrodynamics via Experiment and Simulations

Abstract

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.

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Acknowledgments

Research reported in this publication was supported by the Office of the Director of the National Institutes of Health under Award Number DP5OD019876. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was funded by LDRD 17ERD054 and LDRD 18ERD062 and performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344 (LLNL-JRNL-805606). Computing support for this work came from the LLNL Institutional Computing Grand Challenge Program. This work also used the Extreme Science and Engineering Discovery Environment (XSEDE) resource, Stampede2, at the Texas Advanced Computing Center through Allocation TG-IBN190011.48 The authors acknowledge the Texas Advanced Computing Center (TACC) at The University of Texas at Austin for providing HPC resources that have contributed to the research results reported within this paper.

Conflict of interest

Marianna Pepona, Peter Balogh, Daniel F. Puleri, William F. Hynes, Claire Robertson, Karen Dubbin, Javier Alvarado, Monica L. Moya, and Amanda Randles declare that they have no conflict of interest.

Ethical Approval

No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article.

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Correspondence to Amanda Randles.

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Pepona, M., Balogh, P., Puleri, D.F. et al. Investigating the Interaction Between Circulating Tumor Cells and Local Hydrodynamics via Experiment and Simulations. Cel. Mol. Bioeng. 13, 527–540 (2020). https://doi.org/10.1007/s12195-020-00656-7

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Keywords

  • Hemodynamics
  • Circulating tumor cell
  • Wall shear stress
  • Cell deformability
  • Residence time