Malaria-infected cells stiffen, block blood flow

December 20, 2010
The malaria parasite inside a red blood cell, left, and in a computer-generated model. Malarial infection inhibits the smooth flow of blood through capillaries. Credit: George Karniadakis, Brown University

Although the incidence of malaria has declined in all but a few countries worldwide, according to a World Health Organization report earlier this month, malaria remains a global threat. Nearly 800,000 people succumbed to the mosquito-borne disease in 2009, nearly all of them in the developing world.

Physicians do not have reliable treatment for the virus at various stages, largely because no one has been able to document the malaria parasite's journeys in the body.

Now researchers at Brown University and the Massachusetts Institute of Technology have used advanced computer modeling and laboratory experiments to show how malaria parasites change red blood cells and how the infected cells impede blood flow to the brain and other critical organs.

Their findings, published in the early online edition of the , could help doctors chart, in real time, the buildup in the body of cells infected with malaria or other diseases (such as sickle-cell anemia) and to prescribe treatment accordingly.

"The idea is to predict the evolution of these diseases, just like we predict the weather," said George Karniadakis, professor of applied mathematics at Brown and corresponding author on the paper.

This video is not supported by your browser at this time.
Malaria-infected red blood cells can be 50 times stiffer and have surface changes that disrupt the smooth flow of blood, depriving the brain and other organs of nutrients and oxygen. Credit: George Karniadakis laboratory, Brown University

The researchers worked with , a parasite that can cause by lodging in capillaries of the brain, especially among children. The parasite is found globally but is most common in Africa.

Once introduced into the human body by an infected mosquito's bite, the parasite invades red blood cells. Healthy red blood cells are tremendously elastic; even though they can reach 8 microns in length and 2 microns in thickness, they can easily slide through a capillary just 3 microns in diameter. Capillaries are vital conduits in the human brain and other organs; red blood cells are key transporters of oxygen and nutrients.

Through extensive modeling carried out on one of the world's fastest supercomputers at the National Institute for Computational Sciences, Karniadakis and colleagues found that malaria-infected red blood cells stiffened as much as 50 times more than healthy red blood cells. The result: Infected red blood cells, having lost their elasticity, could no longer pass through capillaries, effectively blocking them.

"Basically what happens is the brain could be deprived of nutrients and oxygen," said Karniadakis, a member of the Center for Fluid Dynamics, Turbulence and Computation at Brown. "This happens because of the deformation of these red blood cells.

"This shows that as stiffening increases (in red blood cells), the viscosity of the blood increases, and the heart has to pump twice as much sometimes to get the same blood flow," Karniadakis added.

The researchers also found that infected red blood cells had a tendency to stick, flip, and flop along the walls of blood vessels — unlike healthy blood cells that flow in the middle of the channel. For reasons not entirely known, the infected develop little knobby protrusions on their cellular skin that tend to stick to the surface of the blood wall, known as the endothelium. Scientists call the sticking cytoadhesion.

"So, what happens is the infected red blood cell is not only stiffer, it's slowed down by this interaction (cytoadhesion)," Karniadakis said. "This drastically changes the flow of blood in the brain, especially in the arterials and in the capillaries."

Explore further: How adhesive protein causes malaria

Related Stories

How adhesive protein causes malaria

September 25, 2007

Researchers at the Swedish medical university Karolinska Institutet (KI) and the Swedish Institute for Infectious Disease Control (SMI) have identified the biochemical mechanism behind the adhesive protein that give rise ...

How the malaria parasite hijacks human red blood cells

July 8, 2008

A new study—done on a scale an order of magnitude greater than anything previously attempted in the field of malaria—has uncovered an arsenal of proteins produced by the malaria parasite that allows it to hijack and remodel ...

Measuring and modeling blood flow in malaria

November 23, 2009

When people have malaria, they are infected with Plasmodium parasites, which enter the body from the saliva of a mosquito, infect cells in the liver, and then spread to red blood cells. Inside the blood cells, the parasites ...

Recommended for you

Genomes uncover life's early history

August 24, 2015

A University of Manchester scientist is part of a team which has carried out one of the biggest ever analyses of genomes on life of all forms.

Rare nautilus sighted for the first time in three decades

August 25, 2015

In early August, biologist Peter Ward returned from the South Pacific with news that he encountered an old friend, one he hadn't seen in over three decades. The University of Washington professor had seen what he considers ...

Why a mutant rice called Big Grain1 yields such big grains

August 24, 2015

(Phys.org)—Rice is one of the most important staple crops grown by humans—very possibly the most important in history. With 4.3 billion inhabitants, Asia is home to 60 percent of the world's population, so it's unsurprising ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.