Numerical Analysis Of Dynamic Behavior And Stress Distribution Of Circulating Tumor Cells With The Effect Of Red Blood Cells In Microvessels

Circulation tumor cells(CTCs)moving in microvessels and transmigrating across venular endothelium is an important step of the cancer metastasis.Inter-cellular interactions between the CTCs and flowing red blood cells(RBCs)and the stress on the CTCs membranes play a critical role in this process.We present a numerical investigation of the dynamic behavior and stress on the CTC membrane in different flow environments.We use the Immersed Boundary Method for modeling and simulating fluid-structure interaction.The blood cells are modeled as elastic capsules enclosing Newtonian fluid with a larger viscosity than the plasma surrounding them,and the thickness of the membranes is neglected.The no-slip boundary condition is applied both on the cells membranes and the vessel walls.In the present work,we analyzed all cases as microcirculatory systems with the diameters of vessels smaller than 30 microns.The simulation results show that the diameters of the vessels,hematocrit(Ht)values,CTCs stiffness and pressure gradient have profound effects both on dynamic behaviors and membrane stress of CTCs.As the Ht increased,the stress on the CTCs membranes would increase with the effect of inter-cellular interactions.It is also found that the interaction between CTCs,RBCs and vascular wall is the major factor to the stress on CTCs membrane when the diameter of blood vessel is less than 20 micron,and the shear rate of flow field is major factor to the stress on CTCs membrane when the diameter of blood vessel is less than 20 micron with Ht=10%.In addition,larger CTCs membrane stiffness and pressure gradient leads to larger stress on the CTCs membranes.The present study provides fundamentals for further researches on the viability,transformation of the phenotype and the extravasation of CTCs under metastasis.