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PhD: Modeling of Blood Circulation and Biochemical Signaling - Ananta Kumar Nayak (LIPhy)

Thesis defence

On December 18, 2023

Ananta Kumar Nayak (LIPhy)

In our body, red blood cells (RBCs) are primarily involved in transporting oxygen and nutrients to the tissues, and conversely, they become the transporter of metabolic excreta such as carbon dioxide from the tissues.  In addition to these passive processes, RBCs are actively participated in communication with the vascular wall. This communication is mediated by a signalling molecule, adenosine triphosphate (ATP), which is released as a result of the shear stress experienced by the RBC membrane.  ATP is known as an energy carrier, and the energy it releases by hydrolysis of the phosphate bond is used to carry out cellular functions. However, the ATP released to the plasma by RBCs triggers a cascade of biochemical reactions in endothelial cells (ECs), resulting in the release of sequestered Ca2+ from the endoplasmic reticulum (ER).  Ca2+ is a ubiquitous ion responsible for numerous cellular functions such as vasodilation, cell proliferation, and gene transcription.  In particular, Ca2+ regulates the synthesis of nitric oxide (NO), an important vasodilator, in the vascular wall. NO molecules act on smooth muscle cells (SMCs), a layer located beneath the endothelium layer, to relax the vessel wall diameter. As a result, increased vessel diameter results in improved blood supply to the area where metabolic needs are high. Nevertheless, the concentration of NO available for SMC relaxation is also affected by RBCs, as they act as scavengers by converting it into other metabolites such as nitrites and nitrates.  Because of the aforementioned importance of RBC dynamics and its impact on biochemical signalling in the vascular wall, it is necessary to understand the fundamentals of local blood perfusion control and progression of vascular diseases. This thesis is mainly devoted to the coupling of RBC dynamics and biochemical signalling occurring in the vascular wall using immersed boundary lattice Boltzmann method (IBLBM). More specifically, we investigated the effect of RBC dynamics in a two-dimensional straight channel (2-D) with changes in parameters such as flow strength, channel width, and RBC concentration on the Ca2+ and NO dynamics. More elaborately, firstly, we developed a minimal homeostatic Ca2+ dynamics model which ensures the return of intracellular Ca2+ concentrations from its non-physiological concentration to the physiological concentration in the presence of agonist (ATP). Secondly, we explicitly integrated ATP released from RBCs and ECs that trigger Ca2+ signalling in the endothelium. This study sheds light on the upstream control of blood perfusion in a vascular network due to the propagation of Ca2+ signals from a region of higher ATP concentration to a region of lower ATP concentration. Lastly, we further modelled both ATP and shear stress-dependent NO synthesis in ECs.  This model is extended to explicitly incorporate the scavenging of NO by RBCs in order to understand NO availability in blood vessels with a 2-D numerical setting. This study highlights the fact that the concentration of NO in the vascular wall strongly depends on the concentration of RBCs.


On December 18, 2023
Complément date



Complément lieu

LIPhy, salle de conférence

Submitted on February 14, 2024

Updated on February 14, 2024