Development of a hybrid fluid-structure interaction (FSI) algorithm to model red blood cell deformation and oxygen-dependent ATP release under flow stresses

The microcirculation serves to deliver oxygen (O 2 ) to tissue as red blood cells (RBCs) pass through the smallest blood vessels in the body: capillaries. Imaging techniques quantify O 2 present in capillaries but lack effective modalities quantifying O 2 entering tissue from capillaries. Thus, mathematical simulation has been used to investigate how O 2 is distributed locally over a variation of metabolic tissue O 2 demands. It has also been used to investigate mechanisms regulating capillary blood flow to meet such demands. Distributed throughout the microcirculation, RBCs have been hypothesized as potential candidates initiating signals at the capillary level that are transmitted upstream to arterioles, thereby altering capillary blood flow. It has been found that RBC deformation, as well as oxyhemoglobin desaturation, can cause release of adenosine triphosphate (ATP). It has been theorized that as RBCs deform with local blood flow, released ATP modulates upstream vessel diameter, but requires mathematical modelling to systematically investigate. A condensed matter model of RBC deformation was developed in the past, with the ability to predict baseline red blood cell shapes (at the micron level), and with the goal of reliably quantifying forces of the RBC on the surrounding environment, owing to its unique elasticity. To investigate how this RBC elasticity interacts with blood flow, the objective of this study was the development of a comprehensive hybrid fluid-structure interaction algorithm. This was done using a novel Discrete Exterior Calculus (DEC) solver for fluid flow, allowing the model to be geometrically versatile. This algorithm was developed to be capable of theoretically simulating RBC deformation in response to a range of shear stress rates in units of [1/ms]. The algorithm allowed detailed tracking of RBC shape changes in response to shear forces (%), osmolarity variations, and membrane tension, making it a powerful tool for understanding the mechanical behavior of RBCs in vivo. Variations in blood flow, and the effect on RBC geometry and shear, are quantified and presented. Using DEC's geometric versatility, fluid simulations through a variety of microvascular geometries will be presented, and deformation parameters will be outlined. Future work includes validation of the algorithm against experimental in vivo data, confirming the accuracy of the model in replicating observed RBC behaviour under varying flow conditions. Furthermore, interpreting the shear response of the RBC to flow in the context of ATP release will be investigated. By quantifying RBC deformation under fluid stresses, and estimating ATP release parameters, a novel approach to understanding how RBCs interact with their microcirculatory environment will be obtained. These findings provide a quantitative framework for understanding how RBCs contribute to microcirculatory regulation and offer a new tool for studying pathophysiological conditions where blood flow and oxygen delivery are compromised. Acknowledgements would like to be given to various NSERC Grants (#R4081A03, CGS-M, CGS-D) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.