Numerical Modelling of the Transport of Cancer Cells*

Cancer metastasis leads to the transport and widespread of malignant cells from the primary tumor to other parts of the body by exploiting body fluids (lymphatic fluid, bloodstream, and interstitial fluid). While the transport of a single cancer cell in fluid flow has been studied in the past, it is unclear how an aggregate of cancer cells (called a tumoroid) deforms and migrates under the impact of hydrodynamic force in vasculature. In this work, we address this knowledge gap by investigating the migration process in a tumoroid in a constricted micro-channel using both experimental and computational methods. Our numerical model is based on a hybrid continuum-particle approach. The cancer cell model includes the cell membrane, nucleus, cytoplasm and the cytoskeleton. The Dissipative Particle Dynamics method was employed to simulate the mechanical components. The blood plasma is modeled as a Newtonian incompressible fluid. A Fluid-Structure Interaction coupling, leveraging the Immersed Boundary Method is developed to simulate the cell's response to flow dynamics. Our computational model allows an accurate estimation of fluid shear stresses on the cell's surface and resolves the local cellular dynamics while providing large-scale flow patterns in the vasculature. Our numerical findings are compared with the accompanied experimental data. Our results suggest that the mechanical response of the tumoroid differs from one of a single cell. We hypothesize that the intracellular and extracellular dynamics response of the multicellular systems is intrinsically linked to their cellular constituents which certain configuration displayed strong resistance to the fluid-induced forces and the ability to migrate in various directions. Our computational framework provides new capabilities for designing bioengineering devices for cell manipulation.