The role of calcium oscillations in the phenotype selection in endothelial cells

• DOI: 10.1038/s41598-021-02720-2
• Publication Date: 2021-12-10T11:03:37Z
• Authors: Birses Debir; Cameron Meaney; Mohammad Kohandel; M. Burcin Unlu
• Keywords: 0303 health sciences; Science; Q; R; Endothelial Cells; Cell Communication; Models, Biological; Article; 03 medical and health sciences; Phenotype; Medicine; Humans; Calcium; Calcium Signaling; Algorithms; Biomarkers; Cells, Cultured; Signal Transduction

Angiogenesis is an important process in the formation and maintenance of tissues which driven by a complex system intracellular intercellular signaling mechanisms. Endothelial cells taking part early angiogenesis must select their phenotype as either tip (leading, migratory) or stalk (following). Recent experiments have demonstrated that rapid calcium oscillations within active characterize this selection these play necessary role governing eventual vessel architecture. In work, we develop mathematical model capable describing then use it to improve our understanding biological mechanisms at play. We developed based on two previously published experimentally validated models resulting simulate various multi-cell scenarios. are able capture essential oscillation dynamics communication between neighboring cells. The results show although late DLL4 (a transmembrane protein activates Notch pathway) levels cell connected with its initial IP3 (Inositol 1,4,5-trisphosphate) level, cell-to-cell determines phenotype.