| As a major constituent of blood (40-50% volume), red blood cells (RBCs) have a pronounced impact on bulk hemorheology via their ability to deform and rotate in response to changes in flow conditions. Previous studies on the dynamic response of RBCs to hydrodynamic forces have been focused primarily on behavior in a linear velocity gradient. Under these conditions, RBCs have been shown to exhibit a rich spectrum of motions such as stretching, tumbling, tank treading, and swinging. Relatively little experimental work, however, has examined how individual RBCs respond to pressure driven flow in more complex conditions. Of particular importance is the extensional flow that occurs at the entrance of an abrupt contraction, which occurs physiologically in cases such as stenoses and aneurysms. Moreover, little is known about how RBCs in various disease states, such as those associated with increased oxidative stress, will respond upon entering a constriction.;In this work, we experimentally investigated the mechanical response of RBCs to the sudden increase in shear stress at the entrance of a narrow constriction. We pumped RBCs through a constriction in an ex vivo microfluidic device and used high speed video to visualize and track the flow behavior of red blood cells. We demonstrate that the majority of RBCs undergo one of four distinct modes of motion: stretching, twisting, tumbling, or rolling. Intriguingly, the majority of RBCs exhibited twisting (rotation around the major axis parallel to the flow direction), a mechanical behavior that is not typically observed in linear velocity gradients. The dynamics of each motion are highly sensitive to the location of the RBC within the channel, and we demonstrate that much of the rotational behavior can be qualitatively rationalized in terms of rigid body rotation. Importantly, we show that RBCs exposed to oxidative stress and RBCs acquired from patients with metabolic syndrome (a disease associated with high levels of oxidative stress) both exhibit significantly altered mechanical dynamics compared to control groups. These findings imply that modifications to the oxidative status of RBCs may have substantial consequences on macroscale hemorheology. |
