2025 Student Poster Prize - 1st Place

Heterogeneity in red blood cell mechanics drives altered blood rheology in sickle cell disease

1. Szafraniec, Hannah M. (University of Minnesota, Department of Biomedical Engineering)
2. Bull, Freya (University College London)
3. Pearce, Philip (University College London)

4. Wood, Dave K. (University of Minnesota)

Abstract

In sickle cell disease (SCD), polymerization of hemoglobin under deoxygenated conditions causes red blood cells (RBCs) to stiffen, resulting in aberrant blood flow. At the continuum level, deoxygenated blood in SCD exhibits increased shear-thinning and wall friction, but it is not understood how the distribution of RBC properties contributes to whole-blood rheology. Therefore, we developed a novel microfluidic platform to probe the effect of oxygen-dependent RBC stiffness and volume fraction on the rheological properties of blood from patients with SCD. Using high-throughput single-cell measurements, we established that oxygen-dependent changes in red blood cell mechanics are highly heterogeneous. In parallel, we measured the effective rheology of the blood from spatially resolved flow fields and found that increases in effective resistances in heterogeneous suspensions were driven by increases in the proportion of stiff cells, similar macroscopically to the behavior of rigid-particle suspensions. To explore mechanisms leading to the emergent rheology, we developed a computational model to simulate confined flow of heterogeneous mixtures of cells. This allowed us to probe the dynamics of the cells and measure the impact on rheology, which we confirmed experimentally. In the presence of deformable cells, the stiffened cells marginate towards channel walls, increasing effective wall friction. In fully deoxygenated conditions in which all cells are stiffened, significant heterogeneity in cell volume fraction along the direction of flow caused localized jamming, drastically increasing effective viscous flow resistance. Overall, our study directly links single cell properties to blood dynamics in microchannels across individual donors and establishes mechanisms for the apparent rheology of heterogeneous mixtures.

1^st Place, 96^th Annual Meeting, Oct 2025, Santa Fe