(117a) Simulations of Red Blood Cells As Oxygen Sensors That Control Blood Flow in Microchannels | AIChE

(117a) Simulations of Red Blood Cells As Oxygen Sensors That Control Blood Flow in Microchannels


Niazi Ardekani, M. - Presenter, Stanford university
Shaqfeh, E., Stanford University
Saadat, A., Stanford University
Wan, J., University of California, Davis
An increase in the neural activity of a normal brain is accompanied by an elevation in local blood flow to satisfy the accelerated demand for glucose and oxygen. This is particularly important in cerebral blood flow due to a limited energy reserve that requires tight neurovascular coupling. The partnership between neural activity and local blood flow is termed functional hyperemia. This regulation in blood flow plays a critical role in functional brain imaging and it is believed that defects in functional hyperemia contribute to cognitive decline in multiple neurodegenerative diseases such as Alzheimer's. The mechanisms behind this tight neurovascular coupling remain elusive to this day despite many decades of research. Recent experimental measurements, however, have identified red blood cells (RBCs) as regulators of brain capillary perfusion[1]. These experiments reveal that RBCs respond to a decrease in local oxygen concentration by increasing their deformability thus leading to an increase in the cell velocity in capillaries. It is hypothesized that the change in deformation occurs due to interactions between deoxygenated hemoglobin inside the cells and band 3 proteins in the RBC membrane. In other words, the amount of stored oxygen inside RBCs controls RBC deformability and therefore its capillary velocity.

Following the results of these recent experiments, a numerical model is developed in this study to capture the purported dynamics of RBCs by varying the cell deformability as a function of stored oxygen inside the cell (Fig. 1). A previously described [2] immersed finite element method combined with a finite-volume incompressible flow solver is employed to determine the dynamics of RBC suspensions while the oxygen transport across the cell interface is modeled as a volumetric absorption/emission process characterized by simple first-order kinetics. Within this model, the oxygen concentration at the cell surface is absorbed/released at a rate described by the reaction rate, k, until equilibrium is reached according to the oxygen-hemoglobin dissociation curve. k is estimated from the reported time duration that cells require to release a certain amount of stored oxygen, which is available from the aforementioned experiments. After the equilibrium is reached, the cell flexibility remains unchanged and no oxygen transport takes place across the cell interface.

Individual RBCs are simulated in a confined duct geometry (with a cross-section of 7.5 × 10 mm) to reproduce the previously reported experimental results. The comparison with the experimental data allows for estimating the shear modulus of the cell membrane, which is the main parameter controlling cell flexibility, for different concentrations of oxygen inside the cell. The results of the simulations show a significant alteration of the shear modulus during the oxygen releasing process, thus emphasizing the importance of considering a variable shear modulus in realistic numerical modeling of RBCs. Moreover, we demonstrate that the deformability of the cell is coupled to the rate of oxygen release –thus an increase in deformability of the cell is accompanied by an increase in oxygen release. This in turn further increases the cell deformability and leads ultimately to a very rapid release of oxygen. Detailed results of the simulations and a comparison with the experimental data[1] will be presented.