Effects of flowing RBCs on adhesion of a circulating tumor cell in microvessels

Abstract

Adhesion of circulating tumor cells (CTCs) to the microvessel wall largely depends on the blood hydrodynamic conditions, one of which is the blood viscosity. Since blood is a non-Newtonian fluid, whose viscosity increases with hematocrit, in the microvessels at low shear rate. In this study, the effects of hematocrit, vessel size, flow rate and red blood cells (RBCs) aggregation on adhesion of a CTC in the microvessels were numerically investigated using dissipative particle dynamics. The membrane of cells was represented by a spring-based network connected by elastic springs to characterize its deformation. RBCs aggregation was modelled by a Morse potential function based on depletion-mediated assumption and the adhesion of the CTC to the vessel wall was achieved by the interactions between receptors and ligands at the CTC and those at the endothelial cells forming the vessel wall. The results demonstrated that in the microvessel of 15μm diameter, the CTC has an increasing probability of adhesion with the hematocrit due to a growing wall-directed force, resulting in a larger number of receptor-ligand bonds formed on the cell surface. However, with the increase in microvessel size, an enhanced lift force at higher hematocrit detaches the initial adherent CTC quickly. If the microvessel is comparable to the CTC in diameter, CTC adhesion is independent of Hct. In addition, the velocity of CTC is larger than the average blood flow velocity in smaller microvessels and the relative velocity of CTC decreases with the increase in microvessel size. An increased blood flow resistance in the presence of CTC was also found. Moreover, it was found that the large deformation induced by high flow rate and the presence of aggregation promote the adhesion of CTC.

Studies of Bending Effects of Microvilli of Leukocyte on Rolling Adhesion

“…Their results indicated that cells with deformations roll much slower and are relatively more stable than those without deformation in shear flow, facts consistent with the experimental findings (9,10). Since then, numerous simulation studies continue to address the process of cell deformation during cellular adhesion (11)(12)(13)(14)(15)(16).…”

Margination and adhesion dynamics of tumor cells in a real microvascular network

“…However, some experiments [ 23 – 25 ] have shown that the soft CTCs are more likely to extravasate from the circulation, because the soft CTCs have a large contact surface with the vascular wall and thus have a higher possibility of adhesion than the rigid CTCs. Recently, some simulation work [ 26 , 27 ] has also favored the latter conclusion.…”

“…A stochastic adhesive model was developed by Hammer and Apte [ 28 ], which has been widely used to theoretically and numerically investigate the adhesion of various cells, certainly including the CTCs [ 27 ]. The model proposed that the cell adhesion is attributed to the dynamic association and dissociation between the receptors on the cell and the ligands on the vessel wall.…”

Modeling of biomechanics and biorheology of red blood cells in type-2 diabetes mellitus

“…Decreased cell deformability and increased cell volume in T2DM have shown significant implications for microcirculatory alterations. Computational modeling and simulations help in predicting how RBCs behave in shear flow and providing insights into how viscous flow transforms RBC shapes, and vice versa, how deformed RBCs distort the surrounding flow (24,42,43,(78)(79)(80)(81)(82). Here, in order to address the effects of cell elasticity and shape on the biorheological behavior of individual T2DM RBCs, we investigate the dynamic behavior of T2DM RBCs in a microfluidic channel with constriction.…”