Mathematical modeling of the capillary-like pattern generated by adrenomedullin-treated human vascular endothelial cells in vitro.
A recently proposed approach was used to model the self-organization into capillary-like structures of human vascular endothelial cells cultured on Matrigel. The model combines a Cellular Potts Model, considering cell adhesion, cytoskeletal rearrangement and chemotaxis, and a Partial Differential Equation model describing the release and the diffusion of a chemoattractant. The results were compared with the data from real in vitro experiments to establish the capability of the model to accurately reproduce both the spontaneous self-assembly of unstimulated cells and their self-organization in the presence of the pro-angiogenic factor adrenomedullin. The results showed that the model can accurately reproduce the self-assembly of unstimulated cells, but it failed in reproducing the adrenomedullin-induced self-organization of the cells. The extension of the model to include cell proliferation led to a good match between simulated and experimental patterns in both cases with predicted proliferation rates in agreement with the data of cell proliferation experiments.
Guidolin
Diego
D
Department of Human Anatomy and Physiology, Section of Anatomy, University of Padova Medical School, Padova, Italy. diego.guidolin@unipd.it
Albertin
Giovanna
G
Sorato
Elisa
E
Oselladore
Barbara
B
Mascarin
Alessandra
A
Ribatti
Domenico
D
D053607:Adrenomedullin / Q000494:pharmacology*; D001483:Base Sequence; D002196:Capillaries / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D017931:DNA Primers / Q000235:genetics; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D010641:Phenotype; D011509:Proteoglycans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D053607:Adrenomedullin; D003094:Collagen; D040262:Receptors, Vascular Endothelial Growth Factor