Red blood cells play a critical role in delivering oxygen to organs by coursing through intricate networks of vessels across cascading bifurcations. In the smallest vessels known as capillaries, the cells need to deform strongly and press against the apex of the vascular bifurcation they cross. Such close contact with the vessel wall can cause some cells to be temporally trapped, namely lingering, at the branching points. The phenomenon of lingering is believed to contribute to the temporal fluctuations of red blood cell distribution in capillary networks, occurring despite typically steady flows of blood into vessels at this scale. However, it has been a puzzle how exactly lingering affects the temporal distribution of red blood cells and under what circumstances red blood cells tend to linger. These are the questions that our study aims to answer. Through carefully designed in vivo experiments with animal models and cell-resolved blood flow simulations on supercomputing facilities, we capture and analyze the lingering behavior of red blood cells under physiological conditions.
The cover art of the April 18 issue of Biophysical Journal combines an in vivo image of the microcirculatory network under microscope and a snapshot from our numerical simulation that highlights the red blood cell dynamics within the reconstructed bifurcations. The simulation snapshot vividly depicts how a red blood cell excessively stretches itself, appearing to linger on the bifurcation apex with a saddle configuration while “pondering” which vessel to enter downstream. Meanwhile, another cell, also strongly deformed, approaches the bifurcation and inevitably interacts with its predecessor before deciding its own way. At this very moment, the trajectory for neither of these two cells is determined, leading to uncertainty in the consequential hematocrit distribution.
Indeed, we reveal that the overall intensity of lingering strongly correlates with deviations in the red blood cell distribution from the established empirical model describing a time-average partitioning pattern. Interestingly, the likelihood of red blood cell lingering was found to be subject to the geometric properties of the vascular bifurcation (e.g., its curvature at the branching point), among other contributing factors such as flow split ratio, cell rigidity, and feeding hematocrit. Beyond the modulating effect of lingering on hematocrit distribution in health, we stress that the lingering mechanism can be considered a pathway to the hindered microcirculatory blood flow under pathological conditions such as malaria, sickle-cell disease, or even COVID-19, for which the mechanical properties (e.g., stiffness) of red blood cells have been found to be markedly altered.
Our study serves as an example of how corroborating experimental-numerical approaches can bring deeper insights into complex phenomena and establish more robust theoretical findings in biophysics or wider natural sciences. To learn more about our research, please visit https://www.uni-saarland.de/lehrstuhl/wagner/publications.html and https://www.biofm-research.com/research.
—Yazdan Rashidi, Greta Simionato, Qi Zhou, Thomas John, Alexander Kihm, Mohammed Bendaoud, Timm Krüger, Miguel O. Bernabeu, Lars Kaestner, Mathias W. Laschke, Michael D. Menger, Christian Wagner, and Alexis Darras