sRBC subpopulations demonstrate increased margination and induce local wall shear stress fluctuations in computational simulations. (A) Angled views of snapshots taken from computational simulations of RBC suspensions composed entirely of hRBCs (left), binary suspensions with a majority of hRBCs and a minority population of sickle RBCs comprising 5% (second) and 10% (third) of the overall suspension, and a suspension composed entirely of sRBCs (right). Each simulation was conducted with a hematocrit of 20%. Because sRBCs have a smaller size than hRBCs, there is a larger number of total RBCs in the 100% sRBC suspension. Binary suspensions were designed to mimic ISCs in individuals with SCD. A CFL can be observed in homogeneous suspensions composed of 100% hRBCs or 100% sRBCs, whereas in binary suspensions, marginated sickle cells are concentrated within the CFL close to channel walls. (B) Steady-state radial hematocrit profiles (Ht) for hRBCs (red) and sRBCs (blue) in RBC suspensions containing 0%, 5%, 10%, and 100% sRBCs, respectively. The x-axis depicts distance from the center of the channel scaled with the radius of a hRBC (scaled radius, r/a), with 0 being the center of the channel and 5 representing the channel walls. In all cases, the hematocrit of the hRBCs as well as sRBCs in the 100% sRBC suspension, drops precipitously close to the wall, corresponding to the CFL. In binary suspensions, sRBCs tend to marginate and travel in higher percentages within the CFL close to channel walls, whereas hRBCs concentrate around the center of the channel. Sickle RBCs in the 100% sRBC suspension did not exhibit the same margination, maintaining the CFL; this can be attributed to the presence of deformable, hRBCs in the binary suspensions, which drive the sRBCs toward the walls. (C) Snapshot of the spatial distribution of additional wall shear stress () induced by hRBCs (left), binary sRBC suspensions comprising 5% (second) and 10% (third) sRBCs and 100% sRBCs (right), respectively. Blue regions indicate large fluctuations and are more numerous in the presence of sRBCs. (D) Probability density profile of excess wall shear stress induced by varying fractions of sRBCs (left). The binary suspensions created large fluctuations in wall shear stress in comparison with the hRBC suspension. The ratio between probability densities (right) shows large positive fluctuations in wall shear stress in binary suspensions of 5% and 10% sRBCs.