Sickle Cell Disease (SCD), also known as sickle cell anemia, is a genetic blood disorder resulted from a single point mutation in the βJglobin gene. The mutation in sickle hemoglobin (HbS) causes binding between the β1 and β2 chains of two HbS molecules when deoxygenated, and this crystallization produces a polymer nucleus, which grows inside the red blood cell (RBC) (1). The HbSpolymerization is believed to damage RBC membrane, decrease the RBC deformability, promote cellular dehydration,and trigger RBC sickling, which leads to vasoJocclusion and impaired blood flow in postcapillaries and small vessels, see Fig. 1. However, there is only limited understanding of the link between thehemoglobin HbS polymerization and the lifeJthreatening painful crises of SCD.
There are different types of sickle cells playing critical roles in the vasoJocclusion process, where the relatively soft sickle cells first adhere to the endothelial walls and the sickled and denseRBCs are more likely to be trapped among the adherent RBCs. With significant heterogeneity of the shape andstiffness evolution of sickle RBCs, the vasoJocclusion appears to be a timeJdelayed/coordinated event among different factors including RBC stiffness, shape and size. These observations point to a fundamental need, in addition to understanding the adhesion process, to characterize the dynamically changing heterogeneous shape and mechanical properties of the sickling RBCs individually and population-wise.