The cell-free layer in simulated microvascular networks

Abstract

In the microcirculation, a plasma layer forms near the vessel walls that is free of red blood cells (RBCs). This region, often termed as the cell-free layer (CFL), plays important haemorheological and biophysical roles, and has been the subject of extensive research. Many previous studies have considered the CFL development in single, isolated vessels that are straight tubes or channels, as well as in isolated bifurcations and mergers. In the body, blood vessels are typically winding and sequentially bifurcate into smaller vessels or merge to form larger vessels. Because of this geometric complexity, the CFL in vivo is three-dimensional (3D) and asymmetric, unlike in fully developed flow in straight tubes. The three-dimensionality of the CFL as it develops in a vascular network, and the underlying hydrodynamic mechanisms, are not well understood. Using a high-fidelity model of cellular-scale blood flow in microvascular networks with in vivo-like topologies, we present a detailed analysis of the fully 3D and asymmetric nature of the CFL in such networks. We show that the CFL significantly varies over different aspects of the networks. Along the vessel lengths, such variations are predominantly non-monotonic, which indicates that the CFL profiles do not simply become more symmetric over the length as they would in straight vessels. We show that vessel tortuosity causes the CFL to become more asymmetric along the length. We specifically identify a curvature-induced migration of the RBCs as the underlying mechanism of increased asymmetry in curved vessels. The vascular bifurcations and mergers are also seen to change the CFL profiles, and in the majority of them the CFL becomes more asymmetric. For most bifurcations, this is generally observed to occur such that the CFL downstream narrows on the side of the vessel nearest the upstream bifurcation, and widens on the other side. The 3D aspects of such behaviour are elucidated. For many bifurcations, a discrepancy exists between the CFL in the daughter vessels, which arises from a disproportionate partitioning between the flow rate and RBC flux. For most mergers, the downstream CFL narrows in the plane of the merger, but widens away from this plane. The dominant mechanism by which such changes occur is identified as the geometric focusing of the two merging streams. To our knowledge, this work provides the first simulation-based analysis of the 3D CFL structure in complex in vivo-like microvascular networks, including the hydrodynamic origins of the observed behaviour.

Abnormal morphology biases haematocrit distribution in tumour vasculature and contributes to heterogeneity in tissue oxygenation

“…Our RBC simulations confirmed previous reports of transient alterations in the CFL downstream of network bifurcations (e.g. asymmetries in the cross-sectional haematocrit profile following a bifurcation [46,47] and the temporal dynamics governing its axisymmetry recovery [37]). Further, for the λ values measured in our tumours and the capillary number considered in our simulations, the CFL did not become symmetric between consecutive branching points.…”

Motion of a capsule in a curved tube

“…There exists no study that systematically addresses such changes in equilibria as inertia is gradually increased. Furthermore, as predicted by Balogh & Bagchi (2019) and discussed previously, particle migration seems to be affected not only by the vessel curvature, but also by the change in curvature. There exists no study that considers the effect of curvature change on migration.…”

“…A somewhat related study is the numerical simulations performed by Balogh & Bagchi (2019) on the flow of red blood cell suspensions in arbitrarily curved vessels in large microvascular networks resembling physiological geometry. They observed that cells move closer to the inner wall (that is, the side with higher curvature) of a vessel.…”

Emergent cell-free layer asymmetry and biased haematocrit partition in a biomimetic vascular network of successive bifurcations

“…These experimental limitations can be potentially overcome by increasingly realistic computational simulations, which can query multiple aspects that are otherwise inconvenient or inaccessible to experiments, such as microscopic cell dynamics in a dense suspension, emergent cell orderings on the crosssectional plane and spatio-temporal RBC flow properties (e.g. evolving CFLs [22,23]).…”