The geometry and mechanical properties of blood-borne particles play a major role in determining their vascular behavior and ability to evade immune cell sequestration. Within this context, the transport dynamics of deformable microcarriers (MCs) in a red blood cell (RBC) suspension is systematically investigated. Trajectories and the margination propensity of nominally spherical particles with five different diameters (DMC = 0.5, 1, 2, 3, and 4 μm) and three levels of deformability (stiff, soft, and extra soft) are studied for two different vessel calibers (capillary: 10 μm; arteriole: 50 μm) under three different hematocrits (Hct = 10%, 20%, and 30%). The multi-component suspension is modeled as elastic membranes and elastic solids representing RBC and MC, respectively, immersed in Newtonian fluid simulated by smoothed particle hydrodynamics method. The results document the existence of two regimes: (i) a “collision force” regime where fast-moving RBCs push sufficiently small particles toward the wall; (ii) a “lift force” regime where sufficiently large particles migrate away from the wall. Between these two regimes, a maximum in margination propensity appears, which depends on the particle size, deformability, and flow conditions. For the considered vessel calibers and hematocrits, 2 μm MC offers the highest margination propensity. The vascular dynamics of small MC (DMC ≤ 0.5 μm) is hardly influenced by their deformability, whereas extra soft MCs behave similarly to RBCs. In addition to the limitations related to the two-dimensional analysis, these simulations suggest that moderately deformable micrometric carriers would more efficiently marginate and seek for vascular targets in the microcirculation.

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