‘Stiff’ cells provide new explanation for differing symptoms in sickle cell patients

(Press-News.org) MINNEAPOLIS / ST. PAUL (02/10/2026) — A new breakthrough study led by researchers at the University of Minnesota Twin Cities could explain why patients with the same genetic sickle cell mutation experience different levels of pain, organ damage and response to treatment.

The study published in Science Advances, shows that 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 stiff cells reorganize themselves within the flow, pushing their way to the edges of blood vessels—a process called margination. This creates significantly more friction and resistance than flexible cells.

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.

"Our work bridges the gap between how single cells behave and how the entire blood supply flows," said David Wood, a professor in the University of Minnesota Department of Biomedical 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".

Using advanced microfluidic "chips" that mimic human blood vessels, the team discovered two key ways flow is disrupted:

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. The team found that these stiff cells begin to appear at oxygen levels as high as 12 percent—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.

"I am really excited we were able to provide greater insight into the physical mechanisms driving the disease," added Hannah Szafraniec, a Ph.D. candidate in the University of Minnesota Department of Biomedical Engineering and lead author on the paper. "This could help the field develop more effective, personalized therapies and new testing for early warning of symptoms."

This new research could help bring more personalized treatments to patients and new testing for early-warning of symptoms. This 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 and Massachusetts General Hospital, and Princeton University. 

The research was funded by the National Heart, Lung, and Blood Institute, which is part of the U.S. National Institutes of Health.

Read the full paper entitled, “Suspension physics govern the multiscale dynamics of blood flow in sickle cell disease,” on the Science Advances’s website.

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