Paper Number
BL9                         My Program 

Session
Biomaterials, Bio-fluid Dynamics and Biorheology

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

Presentation Date and Time
October 20, 2025 (Monday) 2:10

Track / Room
Track 6 / Sweeney Ballroom C

Authors (Click on name to view author profile)

  1. Szafraniec, Hannah M. (University of Minnesota, Department of Biomedical Engineering)
  2. Bull, Freya (University College London)
  3. Higgins, John (Massachusetts General Hospital)
  4. Stone, Howard A. (Princeton University)
  5. Krueger, Timm (University of Edinburgh)
  6. Wood, Dave K. (University of Minnesota)

Author and Affiliation Lines (in printed abstract book)
Hannah M. Szafraniec1, Freya Bull2, John Higgins3, Howard A. Stone4, Timm Krueger5 and Dave K. Wood6
1Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455; 2University College London, London, United Kingdom; 3Massachusetts General Hospital, Boston, MA; 4Princeton University, Princeton, NJ; 5University of Edinburgh, Edinburgh, United Kingdom; 6University of Minnesota, Minneapolis, MN

Speaker / Presenter 
Szafraniec, Hannah M.

Keywords
experimental methods; theoretical methods; computational methods; bio-fluid dynamics; biorheology; methods; microscopy; non-Newtonian fluids; suspensions; techniques

Text of 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.