Dynamics of red blood cell partitioning and flow in in vitro microvascular networks

The microcirculation consists of intricate capillary networks, measuring 5 to 10 μm in diameter, responsible for efficient oxygen delivery and nutrient exchange. Red blood cell (RBC) distribution within these networks is shaped by spatial and temporal dynamics at microvascular bifurcations, including the Zweifach-Fung effect, where RBCs preferentially enter daughter vessels with higher blood flow. However, in larger networks, deviations such as reduced or reversed partitioning occur due to complex RBC behaviors influenced by skewed hematocrit profiles, low feeding hematocrit, and increased flow velocities. Lingering RBCs (LRBCs), which temporarily pause at bifurcation apexes, have been identified as another key factor altering local hematocrit profiles and flow dynamics, yet this phenomenon remains insufficiently studied. Beyond passive RBC flow, neurovascular coupling ensures adequate oxygen delivery during heightened neuronal activity, with pericytes playing a central role in modulating capillary diameter in response to neural signals. While pericytes are suspected to enable localized and rapid blood flow regulation, their contributions in time and space remain debated. Using an in vitro microfluidic model, this study investigates the impact of LRBCs and pericyte activation on RBC distribution and flow dynamics. The first study investigates RBC dynamics at bifurcations using a microfluidic chip with a single diverging bifurcation. After developing a robust classification method for LRBCs, we observed that these cells travel along the centerline in parent vessels but tend to marginate toward the distal wall in daughter vessels. While lingering events did not directly affect local hematocrit partitioning, LRBCs influenced downstream bifurcations by skewing hematocrit distribution. This skewness, linked to the network history effect, highlights the long-range impact of LRBC behavior on reverse hematocrit partitioning. The second study explores the impact of capillary cross-sectional area changes induced by pericyte activation, a mechanism associated with functional hyperemia. By employing a programmable pressure pump to simulate gradual variations in capillary cross-sectional area, we observed that short-term activation increased RBC velocity and hematocrit near the activation site, enhancing localized perfusion. In contrast, prolonged activation caused a network-wide redistribution of RBCs to minimize resistance, ultimately leading to hematocrit depletion due to the Fåhræus effect. These findings highlight the dynamic and adaptive nature of blood flow in capillary vessels, where sustained localized changes can propagate into systemic effects over time. These results suggest that coordinated activation of multiple pericytes and descending arterioles is required to sustain long-time RBC perfusion and prevent systemic imbalances. Together, these studies provide new insights into the interplay between localized flow regulation and systemic capillary network dynamics. They reveal how geometric and dynamic factors influence RBC behavior and perfusion, offering a comprehensive framework for understanding capillary function in both physiological and pathological contexts.

2025

dissertation

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