(A) Experimental results of simultaneous adhesion and polymerization in sickle reticulocytes under hypoxia and shear flow on a fibronectin-coated microchannel wall. (a) (t = 0) The cell adheres on the surface. (d) (t = 7.9 min) During cell adhesion, there is significant protrusion of polymerized HbS fibers (white pointers) outwards of the bulk of the cell. (b,e) Outline of the contours of the initial and final (including the HbS protrusions) snapshots of the adherent sickle reticulocyte. (c,f) Hatched sketches of the cell-wall contact area. The hatched area roughly represents the contact area of the cell’s lipid bilayer. The hatched area in snapshot (c) is approximately two times larger than the hatched area in snapshot (f). The white arrows denote the flow direction. Scale bar: 5 m. From Papageorgiou et al. [116] with permission. (B) Simulation results of HbS polymerization within a mature sickle cell (i) versus a sickle reticulocyte (ii). The excess membrane of the sickle reticulocyte in (ii) (that has not been shed in the circulation yet through vesiculation) allows the polymerized HbS fiber projections to continue to grow outwards of the cell bulk while the membrane is simultaneously encompassing the fibers, i.e., confirming the experimental observations in (A).