Investigating the Interaction Between Circulating Tumor Cells and Local Hydrodynamics via Experiment and Simulations
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Cellular and Molecular Bioengineering, Vol. 13, No. 5, October 2020 (Ó 2020) pp. 527–540 https://doi.org/10.1007/s12195-020-00656-7
2020 CMBE Young Innovators issue
Investigating the Interaction Between Circulating Tumor Cells and Local Hydrodynamics via Experiment and Simulations MARIANNA PEPONA,1 PETER BALOGH,1 DANIEL F. PULERI,1 WILLIAM F. HYNES,2 CLAIRE ROBERTSON,2 KAREN DUBBIN,2 JAVIER ALVARADO,2 MONICA L. MOYA,2 and AMANDA RANDLES 1 1
Department of Biomedical Engineering, Duke University, Durham, NC, USA; and 2Materials Engineering Division, Lawrence Livermore National Laboratory, Livermore, CA, USA (Received 21 February 2020; accepted 25 September 2020; published online 21 October 2020) Associate Editor Scott Simon oversaw the review of this article.
INTRODUCTION
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.
Local hemodynamics play an important role in influencing the location of metastatic sites.22,52 Particular attention has been given to the study of local shear stress due to its relation with the residence time of a CTC at the vessel wall. Given a sufficiently long residence time, a chain of interactions between the CTC and endothelium occurs leading to the formation of adhesive bonds and subsequent extravasation.8,9,49,52 Therefore, knowledge of the hemodynamic factors, in particular the wall shear stress (WSS) distribut
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