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Dynamic deformability of sickle red blood cells in microphysiological flow
Y Alapan1, Y Matsuyama1, J A Little2
1Case Biomanufacturing and Microfabrication Laboratory, Mechanical and Aerospace Engineering Department, Case Western Reserve University, Cleveland, OH 44106, USA.
Technology
|July 21, 2016
Summary
Sickle cell disease (SCD) involves red blood cells (RBCs) with reduced deformability, leading to vaso-occlusion. A new microfluidic method reveals distinct RBC subpopulations in SCD, linking deformability to adhesion and occlusion events.
Area of Science:
- Biomedical Engineering
- Hematology
- Cellular Biology
Background:
- Sickle cell disease (SCD) is characterized by intracellular hemoglobin polymerization, causing red blood cell (RBC) rigidity and adhesion.
- These altered RBC properties contribute to vaso-occlusive events, a hallmark of SCD pathology.
- Understanding RBC biomechanics in SCD is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To develop and validate a microfluidic approach for analyzing the dynamic deformability of adhered red blood cells (RBCs) at the single-cell level.
- To quantify and compare the dynamic deformability and adhesion characteristics of healthy RBCs (HbA) and sickle RBCs (HbS).
- To investigate the relationship between RBC deformability, adhesion, and vaso-occlusion in sickle cell disease.
Main Methods:
- A microfluidic system integrated with a cell dimensioning algorithm was employed to analyze RBCs under controlled microphysiological flow.
- Dynamic deformability was assessed using a novel parameter, the dynamic deformability index (DDI), reflecting time-dependent changes in cell aspect ratio under shear stress.
- Blood samples from 24 subjects, including healthy individuals and SCD patients, were analyzed for RBC adhesion and deformability at various flow shear stresses.
Main Results:
- Sickle hemoglobin (HbS)-containing RBCs exhibited significantly lower dynamic deformability index (DDI) compared to healthy hemoglobin A (HbA)-containing RBCs.
- Subpopulations of sickle RBCs were identified, categorized as deformable and non-deformable, based on their dynamic deformability characteristics.
- A higher number of non-deformable sickle RBCs adhered compared to deformable ones at elevated flow shear stresses, suggesting an interplay between deformability and adhesion in vaso-occlusion.
Conclusions:
- The developed microfluidic approach effectively quantifies dynamic RBC deformability and adhesion at the single-cell level.
- Sickle RBCs display reduced dynamic deformability and exist as distinct deformable and non-deformable subpopulations.
- The findings highlight a critical interplay between altered RBC dynamic deformability and increased adhesion, contributing to vaso-occlusion in sickle cell disease.
