Margination Behavior of a Circulating Cell in a Tortuous Microvessel

In the microcirculation, hydrodynamic interactions between red blood cells (RBCs) and a circulating cell (e.g. leukocyte, cancer cell) can drive the latter to flow next to the vessel wall. This behavior, known as margination, is an essential step in physiology as it precedes cell extravasation from the blood stream and into surrounding tissue. Current understanding of the fluid mechanics influencing margination is based on flow in straight tubes, where a circulating cell will not marginate in absence of RBCs. Recent work has shown a cross-stream wall-directed movement of a deformable cell at low Reynolds number due to vessel curvature. This suggests margination behavior can occur even in absence of RBCs in tortuous microvessels such as that which occurs in vivo. Using high-fidelity 3D cell-resolved simulations, we present a computational study on the margination behavior of a circulating cell flowing through a tortuous microvessel based on in vivo images of the rat mesentery. A long length (1mm) of a 20μm diameter vessel is modeled to capture a wide spectrum of curvature variations, and we simulate transport both with and without RBCs. Hematocrit and shear rate are varied to cover a range of conditions. We quantify mechanistic contributions which influence lateral movement and show how margination can occur either in or out of the curvature plane. We further identify margination under conditions not reported for straight tubes, where RBCs and tortuosity work together to lock the circulating cell near the wall.