IBB Seminar

"Dynamics and Distributions of Cells in Blood Flow"


Michael D. Graham, Ph.D.
Steenbock Professor of Engineering
Harvey D. Spangler Professor
Department of Chemical and Biological Engineering
University of Wisconsin-Madison

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ABSTRACT
As they flow, red blood cells migrate toward the center of a blood vessel, leaving a cell-free layer at the vessel wall, while white blood cells and platelets are preferentially found near the walls, a segregation phenomenon called margination. We present direct simulations of blood flow as well as mechanistic theory that aim to describe and understand these phenomena. We also describe collaborative work with the laboratory of Wilbur Lam that demonstrates the importance of these phenomena in medicine. To disentangle effects of shape, size, and deformability, with first describe direct simulations of multicomponent suspensions of deformable capsules. Observations indicate that margination can be driven by contrasts of size, stiffness or shape – for example, a trace component of stiff or small particles will marginate in a suspension whose majority component is large and soft.   A mechanistic theory predicts, in good agreement with experiments  and our simulations, that the cell-free layer thickness follows a master curve with confinement ratio and volume fraction.  It also predicts several regimes of segregation, depending on the value of a dimensionless “margination parameter” that quantifies the effect of cell-cell collisions as well as hydrodynamic migration of particles away from walls. These segregation phenomena have important physiological and clinical consequences. Treatment of patients with drugs such as dexamethasone or epinephrine lead to softening of white blood cells, and thus to their demargination. In blood disorders such as sickle cell disease and iron deficiency anemia, the aberrant cells are smaller and stiffer than healthy red blood cells, and our simulations predict that these cells will strongly marginate. We also predict that that these marginated cells generate large shear stress fluctuations on the vessel walls, a phenomenon that may explain clinical observations of vascular inflammation in persons with these disorders. 

BIO
Michael D. Graham is the Steenbock Professor of Engineering and Harvey D. Spangler Professor of Chemical and Biological Engineering at the University of Wisconsin-Madison. He received his B.S. in Chemical Engineering from the University of Dayton in 1986 and his PhD. from Cornell University in 1992. After postdoctoral appointments at the University of Houston and Princeton University, he joined the Chemical Engineering faculty at the University of Wisconsin-Madison in 1994. He chaired the department from 2006-2009.

Professor Graham’s research interests include the rheology and dynamics of polymer solutions and suspensions; blood flow in the microcirculation; and instabilities and turbulence in Newtonian and complex fluids. He is author of two textbooks: Microhydrodynamics, Brownian Motion, and Complex Fluids (Cambridge, 2018) and Modeling and Analysis Principles for Chemical and Biological Engineers (Nob Hill, 2013, with James B. Rawlings). 

Among Professor Graham’s professional distinctions are the Best Student Paper Award from the Environmental Division of AIChE in 1986, a CAREER Award from NSF in 1995, the François Frenkiel Award for Fluid Mechanics from the American Physical Society Division of Fluid Dynamics (APS/DFD) in 2004, the Stanley Corrsin Award from APS/DFD in 2015, and a 2018 Vannevar Bush Faculty Fellowship from the US Department of Defense. He has presented many named and plenary lectures, including the inaugural William R. Schowalter Lecture at the 2019 AIChE Annual Meeting.

Professor Graham was an Associate Editor of the Journal of Fluid Mechanics from 2005-2012 and Editor-in-Chief of the Journal of Non-Newtonian Fluid Mechanics from 2013-2015.  He is Past President of the Society of Rheology.