Optical Measurement of Membrane Fluctuations of Sickle Cell Trait Red Blood Cells

Abstract

Sickle cell disease (SCD) is an inherited blood disorder caused by a point mutation in the β-globin gene, Val-His-Leu-Thr-Pro-Glu-Glu-Lys to Val-His-Leu-Thr-Pro-Val-Glu-Lys. This change leads production of Hemoglobin S (HbS) which shows self-assembling in a deoxygenated condition and intensively damages a membrane of red blood cells (RBCs), instead of Hemoglobin A (HbA) which is normal. While individuals having two copies of mutated genes suffers from fatal symptoms including vaso-occlusion and aplastic crisis, individuals having a single copy of HbS and HbA, called sickle cell traits (SCT), do not display the severe symptoms of SCD. Although SCT is typically considered as a benign condition, there are rare cases that present complications. Especially in extreme conditions such as heavy exercise and military training, there are reports of sudden deaths of people with SCT. There are still controversial debates whether individual with SCT have clinical differences compared to normal individuals. Most countries in Sub-Saharan Africa have unusually high populations of people who have sickle genes but most of them are under lack of management. Although worldwide attention is claimed as well as domestic effort, SCD is still major genetic problems and priority of public health in those countries. Due to the limited access of biomedical instruments in Sub-Saharan Africa, simple and cost-effective imaging tools are necessary for in situ study of SCD and SCT. In this work, we quantitatively measured the fluctuation of membranes of red blood cells (RBCs) obtained from individuals with SCD and SCD in Tanzania using quantitative phase imaging unit. Membrane fluctuations over 600 RBCs from 22 individual has been measured. We categorized the whole RBC samples to 4 groups: (1) RBCs from normal individuals, (2) RBCs from SCT individuals, (3) irreversibly sickled RBCs from SCD individuals, and (4) reversibly sickled RBCs from SCD individuals. As widely known, irreversibly sickled RBCs from SCD individuals present weakest fluctuations. We also noticed that SCT RBCs fluctuate similar to that of reversibly sickled RBCs while all HbS-containing RBCs fluctuate less than normal RBCs. This results implies that although the SCT RBCs do not show sickle shape in physiological oxygen level as normal RBCs do, mechanical properties of SCT RBCs is somehow different from normal RBCs and similar to non-sickle RBCs from SCD individuals.