Equation provides new insight into blood flow

Red and white blood cells

Engineers have devised an equation that yields simple predictions as to how quickly blood cells will migrate away from blood-vessel walls, how they will behave when they collide with each other, and how they will segregate during flow.

In the long run, these insights could help practitioners manipulate the mechanics of blood to design better blood transfusions, new techniques for drug delivery, and new processes for isolating blood-borne tumor cells.

Mike Graham, PhD, of the University of Wisconsin-Madison, and his colleagues described this work in Physical Review Letters.

“I’m really excited about this paper because it’s the first analytical theory for this phenomenon,” Dr Graham said. “It’s not very common that theory is ahead of experiments, but we’re in that position now.”

Dr Graham and his colleagues created complex computer simulations that showed how relatively stiff white blood cells and platelets interact with more flexible red blood cells.

As the different cells collide during blood flow, white cells tend to be pushed toward the walls of a blood vessel. This segregation process, called margination, creates some advantages; for example, letting white blood cells quickly exit the blood vessel to head to the site of an injury or infection.

However, the mechanical details of blood could spell both good news and bad in areas ranging from drug delivery to blood disorders to the spread of disease.

“I view my role as providing a fundamental basis of understanding for practitioners and for other engineers who are more directly connected with applications,” Dr Graham said.

Now, he is aiming to draw a firmer connection between mechanical insights and the biological functions they might impact. His group is working to refine the new equation to suit more complex flow situations and pursuing an experimental collaboration with Wilbur Lam, MD, PhD, a hematologist at Georgia Tech and Emory University in Atlanta.

Building on Dr Graham’s theoretical and simulation work, Dr Lam’s research group is creating microfluidic devices to study the behavior of blood cells. Dr Lam has developed a way to grow endothelial cells inside the artificial channels of the microfluidic devices.

“I think, together, our labs have really stumbled on how fluid mechanics may be able to explain a lot of the biological phenomena we see in blood,” Dr Lam said. “This can be related to a new way of understanding inflammation, infections, even transfusion medicine. It really pervades many different problems we see in hematology.”

Dr Graham said that capturing the physical nuances of blood vessels’ shape, size, and relative stiffness has tremendous value, even given the myriad other forces at work in the human body.

“We’d like to be able to convince practitioners that you don’t have to worry about all the details to capture the fundamental understanding of what’s going on,” Dr Graham said. “It’s extremely challenging to incorporate all the phenomena that might be important into a simulation. You have to make your case convincingly—if you want somebody to apply this research—that you’ve kept the important parts.”

Both researchers pointed out that sickle cell anemia has long been understood as both a mechanical and a biological problem. The defective red blood cells the disease causes are not only misshapen, but also stiffer than healthy red blood cells, meaning they block blood flow.

Yet, on a more detailed mechanical level, Drs Graham and Lam believe that sickle cells may literally poke and irritate the inner walls of blood vessels. If so, that would make sickle cell anemia not just a blood disorder but a disorder of the entire circulatory system. Their combined research strengths now create an opportunity to test that hypothesis.

“Biologists and hematologists have known for decades that these cells can get stuck, but what is less understood is that the blood vessel walls in the entire patient are really inflamed, and we don’t really know why,” Dr Lam said.

The researchers noted that a better understanding of blood-flow mechanics could help to make blood transfusions safer as well. Transfusions can sometimes set off heart attacks or lung damage, and the medical community isn’t entirely sure why. Dr Lam wants to find out if certain cells in stored, donated blood have mechanical properties that put patients at greater risk.

Though the collaboration between Drs Graham and Lam is still in an early stage, both researchers see the possibility of opening a new frontier in blood research.

“This would be a whole new category of things we could be looking at, and that’s why it’s so exciting,” Dr Lam said. “Suddenly, we have applications where the mechanics can be just as important.”

Red and white blood cells

Engineers have devised an equation that yields simple predictions as to how quickly blood cells will migrate away from blood-vessel walls, how they will behave when they collide with each other, and how they will segregate during flow.

In the long run, these insights could help practitioners manipulate the mechanics of blood to design better blood transfusions, new techniques for drug delivery, and new processes for isolating blood-borne tumor cells.

Mike Graham, PhD, of the University of Wisconsin-Madison, and his colleagues described this work in Physical Review Letters.

“I’m really excited about this paper because it’s the first analytical theory for this phenomenon,” Dr Graham said. “It’s not very common that theory is ahead of experiments, but we’re in that position now.”

Dr Graham and his colleagues created complex computer simulations that showed how relatively stiff white blood cells and platelets interact with more flexible red blood cells.

As the different cells collide during blood flow, white cells tend to be pushed toward the walls of a blood vessel. This segregation process, called margination, creates some advantages; for example, letting white blood cells quickly exit the blood vessel to head to the site of an injury or infection.

However, the mechanical details of blood could spell both good news and bad in areas ranging from drug delivery to blood disorders to the spread of disease.

“I view my role as providing a fundamental basis of understanding for practitioners and for other engineers who are more directly connected with applications,” Dr Graham said.

Now, he is aiming to draw a firmer connection between mechanical insights and the biological functions they might impact. His group is working to refine the new equation to suit more complex flow situations and pursuing an experimental collaboration with Wilbur Lam, MD, PhD, a hematologist at Georgia Tech and Emory University in Atlanta.

Building on Dr Graham’s theoretical and simulation work, Dr Lam’s research group is creating microfluidic devices to study the behavior of blood cells. Dr Lam has developed a way to grow endothelial cells inside the artificial channels of the microfluidic devices.

“I think, together, our labs have really stumbled on how fluid mechanics may be able to explain a lot of the biological phenomena we see in blood,” Dr Lam said. “This can be related to a new way of understanding inflammation, infections, even transfusion medicine. It really pervades many different problems we see in hematology.”

Dr Graham said that capturing the physical nuances of blood vessels’ shape, size, and relative stiffness has tremendous value, even given the myriad other forces at work in the human body.

“We’d like to be able to convince practitioners that you don’t have to worry about all the details to capture the fundamental understanding of what’s going on,” Dr Graham said. “It’s extremely challenging to incorporate all the phenomena that might be important into a simulation. You have to make your case convincingly—if you want somebody to apply this research—that you’ve kept the important parts.”

Both researchers pointed out that sickle cell anemia has long been understood as both a mechanical and a biological problem. The defective red blood cells the disease causes are not only misshapen, but also stiffer than healthy red blood cells, meaning they block blood flow.

Yet, on a more detailed mechanical level, Drs Graham and Lam believe that sickle cells may literally poke and irritate the inner walls of blood vessels. If so, that would make sickle cell anemia not just a blood disorder but a disorder of the entire circulatory system. Their combined research strengths now create an opportunity to test that hypothesis.

“Biologists and hematologists have known for decades that these cells can get stuck, but what is less understood is that the blood vessel walls in the entire patient are really inflamed, and we don’t really know why,” Dr Lam said.

The researchers noted that a better understanding of blood-flow mechanics could help to make blood transfusions safer as well. Transfusions can sometimes set off heart attacks or lung damage, and the medical community isn’t entirely sure why. Dr Lam wants to find out if certain cells in stored, donated blood have mechanical properties that put patients at greater risk.

Though the collaboration between Drs Graham and Lam is still in an early stage, both researchers see the possibility of opening a new frontier in blood research.

“This would be a whole new category of things we could be looking at, and that’s why it’s so exciting,” Dr Lam said. “Suddenly, we have applications where the mechanics can be just as important.”

Red and white blood cells

Engineers have devised an equation that yields simple predictions as to how quickly blood cells will migrate away from blood-vessel walls, how they will behave when they collide with each other, and how they will segregate during flow.

In the long run, these insights could help practitioners manipulate the mechanics of blood to design better blood transfusions, new techniques for drug delivery, and new processes for isolating blood-borne tumor cells.

Mike Graham, PhD, of the University of Wisconsin-Madison, and his colleagues described this work in Physical Review Letters.

“I’m really excited about this paper because it’s the first analytical theory for this phenomenon,” Dr Graham said. “It’s not very common that theory is ahead of experiments, but we’re in that position now.”

Dr Graham and his colleagues created complex computer simulations that showed how relatively stiff white blood cells and platelets interact with more flexible red blood cells.

As the different cells collide during blood flow, white cells tend to be pushed toward the walls of a blood vessel. This segregation process, called margination, creates some advantages; for example, letting white blood cells quickly exit the blood vessel to head to the site of an injury or infection.

However, the mechanical details of blood could spell both good news and bad in areas ranging from drug delivery to blood disorders to the spread of disease.

“I view my role as providing a fundamental basis of understanding for practitioners and for other engineers who are more directly connected with applications,” Dr Graham said.

Now, he is aiming to draw a firmer connection between mechanical insights and the biological functions they might impact. His group is working to refine the new equation to suit more complex flow situations and pursuing an experimental collaboration with Wilbur Lam, MD, PhD, a hematologist at Georgia Tech and Emory University in Atlanta.

Building on Dr Graham’s theoretical and simulation work, Dr Lam’s research group is creating microfluidic devices to study the behavior of blood cells. Dr Lam has developed a way to grow endothelial cells inside the artificial channels of the microfluidic devices.

“I think, together, our labs have really stumbled on how fluid mechanics may be able to explain a lot of the biological phenomena we see in blood,” Dr Lam said. “This can be related to a new way of understanding inflammation, infections, even transfusion medicine. It really pervades many different problems we see in hematology.”

Dr Graham said that capturing the physical nuances of blood vessels’ shape, size, and relative stiffness has tremendous value, even given the myriad other forces at work in the human body.

“We’d like to be able to convince practitioners that you don’t have to worry about all the details to capture the fundamental understanding of what’s going on,” Dr Graham said. “It’s extremely challenging to incorporate all the phenomena that might be important into a simulation. You have to make your case convincingly—if you want somebody to apply this research—that you’ve kept the important parts.”

Both researchers pointed out that sickle cell anemia has long been understood as both a mechanical and a biological problem. The defective red blood cells the disease causes are not only misshapen, but also stiffer than healthy red blood cells, meaning they block blood flow.

Yet, on a more detailed mechanical level, Drs Graham and Lam believe that sickle cells may literally poke and irritate the inner walls of blood vessels. If so, that would make sickle cell anemia not just a blood disorder but a disorder of the entire circulatory system. Their combined research strengths now create an opportunity to test that hypothesis.

“Biologists and hematologists have known for decades that these cells can get stuck, but what is less understood is that the blood vessel walls in the entire patient are really inflamed, and we don’t really know why,” Dr Lam said.

The researchers noted that a better understanding of blood-flow mechanics could help to make blood transfusions safer as well. Transfusions can sometimes set off heart attacks or lung damage, and the medical community isn’t entirely sure why. Dr Lam wants to find out if certain cells in stored, donated blood have mechanical properties that put patients at greater risk.

Though the collaboration between Drs Graham and Lam is still in an early stage, both researchers see the possibility of opening a new frontier in blood research.

“This would be a whole new category of things we could be looking at, and that’s why it’s so exciting,” Dr Lam said. “Suddenly, we have applications where the mechanics can be just as important.”