AsianScientist (Apr. 12, 2017) – An international team of researchers has developed a method to measure the ability of red blood cells to deform and return to their original shape. Their results, published in Scientific Reports, may lead to an improved diagnosis of blood-related diseases such as septic shock and malaria.
Red blood cells, also called erythrocytes, need a certain springiness to circulate through the body. Some blood vessels are smaller than the diameter of an erythrocyte, forcing the cells to fold as they squeeze through.
To study how erythrocytes spring back into shape after deforming to pass through a constriction, an international team of researchers centered at Osaka University built what they call a “Catch-Load-Launch” microfluidic platform.
The experimental setup included a microchannel, in which a single erythrocyte could be held in place for any desired length of time before being launched into a wider section using a robotic pump, simulating the transition from a capillary into a larger vessel.
“The cell was precisely localized in the microchannel by the combination of pressure control and real-time visual feedback,” said study coauthor Professor Makoto Kaneko. “This let us ‘catch’ an erythrocyte in front of the constriction, ‘load’ it inside for a desired time, and quickly ‘launch’ it from the constriction to monitor the shape recovery over time.”
Each erythrocyte has an internal cytoskeleton made of interlinking networks of filaments, including spectrin proteins, that contributes to its rigidity. Dynamic remodeling of this scaffold as the erythrocyte changes shape requires the cell to expend fuel, usually adenosine triphosphate (ATP).
The researchers found that as the time the erythrocyte was held in the constricted region was increased—from five seconds all the way to five minutes—the time it took the cell to recover its normal shape also increased. For very short constriction times, the cells bounced back within 1/10 of a second. Conversely, it took approximately ten seconds for cells to recover if they were held in the narrow segment longer than about three minutes.
The researchers next studied how the red blood cells’ recovery time was affected by a lack of ATP. Contrary to intuition, cells deprived of this fuel, ATP, took less time to recover.
Finally, the “Catch-Load-Launch” system was used to study the life-threatening condition known as septic shock. This can occur when bacteria invade the bloodstream and release endotoxins, which are known to affect cytoskeleton proteins. Patients in septic shock may suffer from reduced circulation inside the narrow blood vessels as the erythrocytes become too stiff. The same problem can be caused by Plasmodium falciparum, the parasite responsible for malaria.
The researchers exposed red blood cells to endotoxin from the bacteria Salmonella minnesota and found the erythrocytes became stiffer and less resilient, like those starved of ATP.
“There is a great deal of evidence that relates certain diseases, including sepsis and malaria, to a decrease in the deformability of red blood cells,” said lead author Professor Hiroaki Ito. “Such a stiffening can lead to a disturbance in microcirculation, and our ‘Catch-Load-Launch’ platform has the potential to be applied to the mechanical diagnosis of these diseased blood cells.”
The article can be found at: Ito et al. (2017) Mechanical Diagnosis of Human Erythrocytes by Ultra-high Speed Manipulation Unraveled Critical Time Window for Global Cytoskeletal Remodeling.
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Source: Osaka University.
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