Effect of Magnetic Field and Magnetic Nanoparticles on Choice of Endothelial Cell Phenotype

Background. Endothelial cells as participants in angiogenesis choose their phenotype as tip cells (leading, migratory) or stalk cells (following). It has been experimentally found and theoretically modeled that rapid oscillations in intracellular calcium concentration play a key role in controlling phenotype selection and possible vessel architecture. In addition, the intracellular calcium concentration in endothelial cells is known to be regulated by mechanical wall shear stress induced by blood flow, which controls mechanosensitive calcium ion channel gating. Experimental methods of controlling mechanosensitive ion channel gating in external magnetic fields with application of magnetic nanoparticles are developed that affect magnetic nanoparticles artificially attached to cell membranes. Objective. A key question is raised about the possibility of controlled selection of endothelial cell phenotype in external magnetic fields due to the presence of artificial or biogenic magnetic nanoparticles embedded in the cell membrane. Methods. The magnetic wall shear stress is calculated due to the influence of the external magnetic field on the magnetic nanoparticles embedded in the cell membrane, which controls the mechanosensitive calcium ion pathways. Numerical modeling of oscillations in intracellular calcium concentration in endothelial cells and determination of their final phenotype was carried out taking into account intercellular communication. The python programming language and scipy, py-pde, matplotlib packages of the python programming language were used for numerical modeling. Results. The magnetic field flux density and frequency ranges of a uniform rotating magnetic field, as well as the magnitude of the gradient and the frequency of a non-uniform oscillating magnetic field were calculated for controlling the amplitude and frequency of intracellular calcium concentration oscillations in endothelial cells, as well as the selection of their phenotype. It opens the perspective of controlling angiogenesis and vessel architecture. Conclusions. Phenotype selection by endothelial cells can be controlled in a uniform rotating external magnetic field, as well as in a non-homogeneous oscillating magnetic field.