A numerical study of tumor cell arrest in microvessels qualifying for mechanical entrapment

Abstract

During hematogenous metastasis, the arrest of tumor cells in the microvasculature is a prerequisite for extravasation from the circulation to a distant host organ. To reveal such arrest behavior, we implement three-dimensional numerical simulations on the motion of a single tumor cell in microvessels at the cellular scale and mainly investigate the interactions among mechanical entrapment, adhesion, and cell stiffness, and their effects on the tumor cell arrest. Two types of vascular configurations qualifying for mechanical entrapment are considered, the constriction and bifurcation structures that are comparable in diameter with the tumor cell. The main results indicate that in the constriction tube, as the constriction radius is increased, the tendency that number of adhesion bonds increases with increasing shear modulus becomes more and more obvious. However, the adhesion behavior has little effect on the tumor cell arrest in the constriction region, regardless of the number of adhesion bonds. The mechanical entrapment plays a more important role than the cell stiffness in the tumor cell arrest in the constriction tube. In the bifurcated tube, the tumor cell is more likely to be arrested in the bifurcation region with a small bifurcation angle. Moreover, as the bifurcation angle or shear modulus is decreased, the effect of adhesion behavior on the tumor cell arrest becomes increasingly obvious. These results are helpful in understanding the biomechanism of tumor metastasis.