PHILADELPHIA — For decades, researchers thought that blood plasma behaved like water. But, according to new research from the University of Pennsylvania and Saarland University in Germany, plasma is more elastic and viscous than water, and, like ketchup, its flow properties depend on the pressure it is under. These traits mean that blood plasma has a much greater effect on how blood flows than was previously thought.

The study may help improve researchers’ understanding of medical conditions such as thrombosis, aneurysms and arteriosclerosis. It may also lead to more accurate computer simulations of blood, or even to better artificial blood substitutes.   

Professor Paulo Arratia of Penn’s School of Engineering and Applied Science’s Department of Mechanical Engineering and Applied Mechanics collaborated with Saarland University physicist Christian Wagner to experimentally demonstrate blood plasma’s previously misunderstood traits.

Their work was published in the journal Physical Review Letters.

Whole blood is a “non-Newtonian fluid,” a fluid that has flow properties that change depending on conditions. Blood, like ketchup, is a “shear thinning fluid” in that it becomes less viscous with increasing pressure, enabling it to flow into the narrowest of capillaries. The flow properties of water are, in contrast, essentially constant.

Blood’s flow characteristics were assumed to be mainly due to the presence of red blood cells, which account for almost half of blood’s volume. The liquid that makes up most of the remaining volume — the blood plasma — is 92 percent water.

“Nobody thought plasma could be a complex fluid,” Arratia said. “We thought it just behaved like water because, for the most part, it does. But plasma has its own proteins in it — beyond the red blood cells, white blood cells and platelets in whole blood — that are biopolymer molecules. And we thought, every time you have molecules like that, you end up with a non-Newtonian fluid.”

To test whether blood plasma was by itself non-Newtonian, Wagner and Arratia’s research teams studied its flow dynamics using several types of experiments. The research conducted at Saarland University involved experiments in which the blood plasma was allowed to form drops inside a specially built apparatus equipped with high-speed cameras. These cameras were fitted with high-resolution microscope lenses to analyze the drops’ shape in fine detail. This close examination revealed the plasma’s “viscoelastic” properties, which means that it exhibited both viscous and elastic behavior when deformed.

“Our experiments showed that the blood plasma forms threads,” Wagner said. “That is, it exhibits an extensional viscosity, which is something we do not observe in water.” 

Arratia’s team at Penn, which includes graduate students Lichao Pan and Mike Garcia, developed a microfluidic system in order to study the flow properties of blood plasma in a context more resembling the vascular system. Their measurements showed that blood plasma exhibits a flow behavior different to that of water and that plasma can demonstrate a substantially higher flow resistance.

“An important part of our study was developing microfluidic instruments sensitive enough to pick up the small differences in viscosity that are the signature of non-Newtonian fluids,” Arratia said.

Wagner’s team also showed that blood plasma influences the creation of vortices in flowing blood. These vortices may facilitate the formation of deposits on blood vessel walls, which could influence blood clot formation. In one of their experiments, the research team let plasma flow through a narrow channel of the kind found in constricted arteries or in a stent. Vortical structures were detected at both the entrance and exit of the narrow channel, which resulted from the viscoelastic flow properties of blood plasma.

“Although we found that blood plasma is only a weak non-Newtonian fluid, even that little bit of elasticity can really alter the flow under certain conditions,” Arratia said. “In our circulatory system, for example, you have a lot of instances where you go through contractions and expansions, like from a big vein into a little capillary, or going through a clot where the flow is constricted.” 

Beyond its relevance to understanding various cardiovascular diseases, filling in all of the details responsible for how whole blood behaves is a critical step for many practical applications.

“If you want to make synthetic blood, for example, you have to reproduce all of the components exactly to make a good product,” Arratia said. “It all matters.”

The research at the University of Pennsylvania was supported by the National Science Foundation through its Chemical, Bioengineering, Environmental and Transport Systems program. The research at Saarland University was performed within the Research Training Group called Structure Formation and Transport in Complex Systems funded by the German Research Foundation.