Cell mechanics: Motion of the microscopic

By Hayley Raj

It may be hard to imagine that the microscopic cells in our blood follow specific patterns of flow, and that this may have important physiological consequences, but Professor Mike Graham is focusing his research on this very concept. Graham, a professor in the Department of Chemical and Biological Engineering at the University of Wisconsin-Madison, presented on September 27, 2019 at the Mechanics Seminar Series. In his talk, “Blood, bacteria, and boundary integrals: dynamics of cells in flow,” Graham spoke about the phenomenon of margination, in which certain cell types move towards blood vessel walls as they flow. Normally, red blood cells tend to flow along the centerline, while white blood cells congregate towards the vessel edges. Graham’s research group, motivated to learn more about the mechanics of this process, developed a theory to predict the dynamics of various cell types. They investigated the effects of mechanical properties such as cell size, rigidity, and shape on margination, and found that stiffer cells tend to migrate towards vessel walls, while softer cells flow at higher speeds through the center of the vessel. This margination is in part due to collisions between the cells during flow.

These findings could provide insight into the mechanisms of healthy and disease states. For example, it is possible that changes in leukocyte stiffness may contribute to the recruitment of white blood cells to the vessel walls during the inflammatory response. It is also known that endothelial cell damage occurs in people with sickle cell disease. Graham says that it is possible that these abnormal red blood cells, which tend to be rigid, cause damage as a result of their migration towards vessel walls (called margination). Some of his early simulations provide evidence that this may be true.

So how has Graham approached this investigation? First, his research group developed a theory to describe margination in blood flow, based on principles of fluid dynamics and suspension transport. They were then able to run simulations and physical experiments to validate their work. The advantage of developing this type of theory is that they can tease apart the effects of different mechanical variables on the degree of margination.

Graham’s research into cell dynamics does not end with blood cells, however. Using simulations, his group has also investigated the effects of flagellar stiffness on the swimming patterns of bacteria. They have found that in uniflagellar bacteria, greater stiffness of the protein that connects the flagellum to the cell body imparts greater stability. However, the opposite is true for multiflagellar bacteria that swim chaotically when protein stiffness is high.

Graham plans to continue this line of research moving forward. Whether it is the effect of various drugs on white blood cell flow patterns or the mechanical properties that allow bacteria to thrive inside the body, he believes that there is much more we can learn from the dynamics of cells.