Margination behavior of a circulating cell in a tortuous microvessel

Abstract

In the mammalian microcirculation, circulating cells (CCs) such as white blood cells or cancer cells can be forced to flow alongside the vessel wall through hydrodynamic interactions with red blood cells (RBCs). This phenomenon, known as margination, plays an important role in physiology as it precedes the extravasation of a CC from the bloodstream into surrounding tissue. Current knowledge of the fluid mechanics influencing margination is primarily based on idealized straight tube flow. Microvessels in vivo, however, are often observed to be tortuous, and the influence of this morphology on CC margination is largely unknown. In the current work, we utilize high-fidelity three-dimensional (3D) cell-resolved simulations to study the margination behavior of a CC flowing with RBCs through a tortuous microvessel over a range of conditions typical of the microcirculation. We observe cross-stream lateral CC movement in response to local curvature, which generally augments the ability of the CC to reach the near-wall region. Once the CC marginates, the presence of RBCs in the central region tends to lock the CC in the near-wall cell-free layer. The overall impact of tortuosity on the degree of margination, however, is mixed. At low hematocrit, tortuosity provides a fluid dynamics-derived mechanism to grant CCs access to near-wall locations under conditions where this behavior generally does not occur in a straight tube. At higher hematocrit where a CC can easily marginate in a straight tube, the varying local curvature causes intermittent motion away from the wall thus slightly reducing the degree of margination.