Collide and conquer: How blood cells sort themselves out

In human blood, red blood cells barrel through the center of the blood vessels, while in a phenomenon known as margination, platelets and white blood cells hug the vessel walls, ready to emerge into the body to fight an injury or infection.

Given the role of platelets and white blood cells as vital contributors to human health, this margination is an important natural process with clear benefits-yet until now, researchers lacked understanding of how it happens.

Through mathematical modeling and computer simulations, University of Wisconsin–Madison chemical and biological engineers discovered that when stiff white blood cells and platelets collide with the more flexible red blood cells during blood flow, red blood cells push the white blood cells and platelets aside, while not moving much themselves. As a result, white blood cells and platelets ultimately are “trapped” near the vessel walls.

The advance could, for example, increase physicians’ understanding of bleeding disorders and diseases such as anemia and malaria or inform the ways in which researchers design particles that deliver cancer-fighting drugs to tissue via the bloodstream.

Michael Graham, the Harvey D. Spangler professor of chemical and biological engineering at UW–Madison, and Amit Kumar, a UW–Madison chemical and biological engineering postdoctoral researcher, published their findings in the Sept. 7, 2012, issue of the journal Physical Review Letters.

Blood is a multicomponent suspension, and the researchers’ expertise in complex fluid flows and computer simulation was vital to the research, says Graham. “Platelets and white blood cells differ in many ways from red blood cells,” he says. “In an experiment, you can’t tune their properties, and so you can’t do a controlled study.”

Simulation, however, enabled Graham and Kumar to control cell stiffness and determine its effect on collisions between cells. Using Kumar’s mathematical model-which incorporates key particle transport mechanisms in suspensions-they also verified that collisions between flexible red blood cells and stiff platelets or white blood cells are important in margination.

“We’ve gained some understanding of a very fundamental process that happens in blood flow,” says Graham.

He and members of his research group now are studying the effects of particle shape and size on collisions and margination. They are pursuing collaborations with clinicians to explore potential medical applications of their advance. While drug-delivery particle design is one application, they also could apply their knowledge in, for example, improving microfluidic devices that separate blood components and are useful for treating leukemia or in platelet-rich plasma therapy.

Graham and Kumar received funding for their research from the National Science Foundation, in part through the American Recovery and Reinvestment Act.