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Deciphering circulating tumor cells binding in a microfluidic system thanks to a parameterized mathematical model.

Giorgia Ciavolella1, Julien Granet2, Jacky G Goetz3

  • 1Institut Denis Poisson, Université d'Orléans, CNRS, Université de Tours, 45067 Orléans, France.

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Summary

This study models circulating tumor cell (CTC) behavior in blood flow, revealing how fluid dynamics and protein interactions influence metastasis spread. The findings enable predicting CTC trajectories and developing digital twins for flowing cells.

Keywords:
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Area of Science:

  • Biophysics
  • Cancer Biology
  • Fluid Dynamics

Background:

  • Metastasis spread remains incompletely understood, particularly the behavior of circulating tumor cells (CTCs) in bloodstream.
  • Understanding CTCs' interaction with endothelial layers is vital for metastasis research.

Purpose of the Study:

  • To characterize the trajectories of CTCs under hemodynamic and adhesion forces.
  • To quantify the influence of fluid velocity and protein depletions on CTC adhesion.

Main Methods:

  • Utilized in vitro microfluidic device measurements of CTCs interacting with endothelial layers.
  • Developed a combined differential equation model (Poiseuille flow, ODE adhesion model) with a calibration procedure.
  • Reconstructed unknown fluid velocity profiles crucial for accurate cell trajectory analysis.

Main Results:

  • Quantified the significant impact of fluid velocity on CTC adhesion dynamics.
  • Confirmed the role of specific proteins in decelerating CTCs, validating model predictions.
  • Successfully generated synthetic CTC trajectories for unobserved experimental conditions.

Conclusions:

  • The developed model accurately predicts CTC trajectories by integrating fluid dynamics and cell adhesion.
  • This approach provides a foundation for a digital twin of flowing cells, aiding metastasis research.
  • Highlights the critical interplay between blood flow and cellular interactions in cancer progression.