Infection with parasites changes the shape of RBCs resulting in cells becoming stuck in brain blood vessels.
This finding may provide an alternative way to combat malaria that could lead to new drug targets to help RBCs resist being transformed during infection.
Published in the Proceedings of the National Academy of Sciences of the United States of America (PLOS) today, Professor Leann Tilley from the University of Melbourne and the Bio21 Institute said lifegiving RBCs are turned into potential killers upon invasion by malaria parasites.
A red blood cell travels 500 kilometres during its four-month lifespan. During each circulation of the body, the RBC squeezes through capillaries whose width is only about one quarter of RBC’s resting diameter and is exposed to high turbulence in the arteries.
To survive this marathon, the RBC needs a very special membrane structure around the cell that is flexible enough to change shape but resilient enough to avoid damage.
“When an RBC becomes infected with the malaria parasite, the properties of the RBC change. The infected RBC becomes quite rigid and the cells stick to the walls of the host’s blood vessels. Accumulation in capillaries in organs such as the brain causes the severe symptoms associated with cerebral malaria,” Professor Tilley said.
Cerebral malaria occurs mainly in children. It is a complication that occurs when parasites stick to blood vessels in the brain. It causes coma and once it is initiated, even with the best possible treatment, 10-20 per-cent of patients die.
Until now, it was not understood how the parasite that is growing inside the RBC makes its host cell so rigid. To better understand this, Professor Leann Tilley worked with Prof Sulin Zhang from PennState University, and colleagues from the Massachusetts Institute of Technology and Carnegie Mellon University,USA.
As physicists and engineers, the collaborators are very good at understanding complex biomechanical problems. The work shows the value of physical and biological scientists working together to provide new solutions to medical problems.
“The engineers created a sophisticated mathematical model that describes how all the components work together,” she said.
The mathematical model explains how subtle changes to the molecular structure of the RBC membrane can change its ability to undergo deformation. It also explains how the rigidification of the host RBC membrane helps infected RBCs stick to blood vessel walls.The team is hopeful that this new understanding will help design drugs that block the parasite-induced rearrangements of the RBC .
“The recent revolution in computational methods provides exciting and efficient new approaches that can be used to solve complex problems.”
Source: University of Melbourne