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Image Credit: University of Minnesota
Scientific Frontline: Extended "At a Glance" Summary
The Core Concept: Researchers have determined that the severity of sickle cell disease (SCD) symptoms is driven by the specific physical behavior of a small sub-population of rigid red blood cells, rather than the average "thickness" or viscosity of the patient's blood as previously believed.
Key Distinction/Mechanism: Contrary to traditional "bulk" measurements that average cell properties, this research reveals that stiff cells physically reorganize within the bloodstream. Through a process called margination, these rigid cells push toward the edges of blood vessels, significantly increasing friction against vessel walls. At higher concentrations, this leads to localized jamming, creating sudden spikes in flow resistance. Notably, these stiff cells begin to appear at oxygen levels as high as 12%—levels found in the lungs and brain—suggesting vessel blockages can initiate much earlier in the oxygen-depletion process than previously thought.
Major Frameworks/Components:
- Microfluidic Modeling: The use of advanced chips designed to mimic the geometry and flow dynamics of human blood vessels.
- Margination: The tendency of stiff particles (cells) to migrate toward vessel walls during flow.
- Fractional Analysis: A shift from analyzing whole-blood averages to measuring the specific fraction and behavior of individual rigid cells.
Branch of Science: Biomedical Engineering, Biophysics, Hematology, and Rheology.
Future Application:
- Personalized Diagnostics: New tests that predict disease severity and pain crises by measuring the fraction of stiff cells rather than genetic markers alone.
- Therapeutic Targets: Development of treatments specifically designed to prevent cell stiffening or margination.
- Broader Disease Modeling: Application of these fluid dynamic principles to other conditions involving blood flow changes, such as malaria, diabetes, and certain cancers.
Why It Matters: This research resolves a critical clinical paradox: why patients with the exact same genetic sickle cell mutation experience vastly different levels of pain, organ damage, and life expectancy. By identifying the physical mechanism of blood flow disruption, it provides a more accurate predictor of clinical outcomes than current methods, potentially leading to more effective, individualized patient care.
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| Stiff cells organize within the flow, creating low (left) concentration regions and high (right) concentration regions, which drastically increases flow resistance. Image Credit: Hannah Szafraniec |
A breakthrough study led by researchers at the University of Minnesota could explain why patients with the same genetic sickle cell mutation experience different levels of pain, organ damage and response to treatment.
Sickle cell disease is an inherited lifelong disorder that affects millions worldwide, causing red blood cells — which are normally flexible and doughnut-shaped — to become stiff and crescent-shaped in low-oxygen environments. This leads to blockages, excruciating pain and reduced life expectancy. Traditionally, blood has been tested using "bulk" measurements that average out the properties of all cells, often missing the subtle but critical differences between individual cells.
The study, published in Science Advances, used advanced microfluidic “chips” that mimic human blood vessels to see how blood flow is disrupted by different types of stiff blood cells. They found:
The severity of sickle cell disease is not best predicted by the average “thickness” of a patient’s blood, but by the specific behavior of a small population of highly stiff red blood cells. These cells reorganize themselves within the flow, pushing their way to the edges of blood vessels. This creates significantly more friction and resistance than flexible cells.
Blood flow is disrupted in two key ways:
- Margination: Even a small number of stiff cells can move to the vessel walls, drastically increasing wall friction.
- Localized Jamming: At higher concentrations, stiff cells can cause the blood to "jam" in specific areas, creating a sudden and dramatic increase in flow resistance.
Stiff cells begin to appear at oxygen levels as high as 12% — levels typically found in the lungs and brain. This suggests that the physical processes leading to vessel blockages can start much earlier in the oxygen-depletion process than previously thought.
"Our work bridges the gap between how single cells behave and how the entire blood supply flows," said David Wood, a professor in the College of Science and Engineering and senior author of the study. "By using an engineering approach to measure both individual cell properties and whole blood dynamics, we found that patients with very different clinical profiles all follow the same underlying physical relationship governed by the fraction of stiff cells."
"I am really excited we were able to provide greater insight into the physical mechanisms driving the disease," said Hannah Szafraniec, a Ph.D. candidate in the College of Science and Engineering and lead author on the paper. "This could help the field develop more effective, personalized therapies and new testing that can give early warning for symptoms of sickle cell disease.”
The research could also be applied to other blood-related disorders, including malaria, diabetes and certain cancers.
In addition to Wood and Szafraniec, the study was done in collaboration with University College of London, University of Edinburgh, Harvard University, Massachusetts General Hospital and Princeton University.
Funding: The research was funded by the National Heart, Lung, and Blood Institute, which is part of the U.S. National Institutes of Health.
Published in journal: Science Advances
Title: Suspension physics govern the multiscale dynamics of blood flow in sickle cell disease
Authors: Hannah M. Szafraniec, Freya Bull, John M. Higgins, Howard A. Stone, Timm Krüger, Philip Pearce, and David K. Wood
Source/Credit: University of Minnesota
Reference Number: bmed021126_01
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