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Cellular and Molecular Bioengineering

, Volume 12, Issue 6, pp 543–558 | Cite as

Unraveling the Vascular Fate of Deformable Circulating Tumor Cells Via a Hierarchical Computational Model

  • Pietro Lenarda
  • Alessandro Coclite
  • Paolo DecuzziEmail author
Article

Abstract

Introduction

Distant spreading of primary lesions is modulated by the vascular dynamics of circulating tumor cells (CTCs) and their ability to establish metastatic niches. While the mechanisms regulating CTC homing in specific tissues are yet to be elucidated, it is well documented that CTCs possess different size, biological properties and deformability.

Methods

A computational model is presented to predict the vascular transport and adhesion of CTCs in whole blood. A Lattice–Boltzmann method, which is employed to solve the Navier-Stokes equation for the plasma flow, is coupled with an Immersed Boundary Method.

Results

The vascular dynamics of a CTC is assessed in large and small microcapillaries. The CTC shear modulus \({k}_{\text{ctc}}\) is varied returning CTCs that are stiffer, softer and equally deformable as compared to RBCs. In large microcapillaries, soft CTCs behave similarly to RBCs and move away from the vessel walls; whereas rigid CTCs are pushed laterally by the fast moving RBCs and interact with the vessel walls. Three adhesion behaviors are observed—firm adhesion, rolling and crawling over the vessel walls—depending on the CTC stiffness. On the contrary, in small microcapillaries, rigid CTCs are pushed downstream by a compact train of RBCs and cannot establish any firm interaction with the vessel walls; whereas soft CTCs are squeezed between the vessel wall and the RBC train and rapidly establish firm adhesion.

Conclusions

These findings document the relevance of cell deformability in CTC vascular adhesion and provide insights on the mechanisms regulating metastasis formation in different vascular districts.

Keywords

Lattice–Boltzmann method Immersed Boundary method Cell mechanics 

Notes

Acknowledgments

This project was partially supported by the European Research Council, under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant Agreement No. 616695, by the Italian Association for Cancer Research (AIRC) under the Individual Investigator Grant No. 17664, and by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska–Curie Grant Agreement No. 754490.

Conflict of interest

Dr. Lenarda, Dr. Coclite and Dr. Decuzzi declare that they have no conflicts of interest.

Research Involving Human and Animal Rights

No animal studies or experiments with human samples were carried out by the authors for this article.

Supplementary material

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Copyright information

© Biomedical Engineering Society 2019

Authors and Affiliations

  1. 1.Laboratory of Nanotechnology for Precision MedicineFondazione Istituto Italiano di TecnologiaGenoaItaly

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