title: In-silico patterning of vascular mesenchymal cells in three dimensions.
abstract: Cells organize in complex three-dimensional patterns by interacting with proteins along with the surrounding extracellular matrix. This organization provides the mechanical and chemical cues that ultimately influence a cell's differentiation and function. Here, we computationally investigate the pattern formation process of vascular mesenchymal cells arising from their interaction with Bone Morphogenic Protein-2 (BMP-2) and its inhibitor, Matrix Gla Protein (MGP). Using a first-principles approach, we derive a reaction-diffusion model based on the biochemical interactions of BMP-2, MGP and cells. Simulations of the model exhibit a wide variety of three-dimensional patterns not observed in a two-dimensional analysis. We demonstrate the emergence of three types of patterns: spheres, tubes, and sheets, and show that the patterns can be tuned by modifying parameters in the model such as the degradation rates of proteins and chemotactic coefficient of cells. Our model may be useful for improved engineering of three-dimensional tissue structures as well as for understanding three dimensional microenvironments in developmental processes.
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Tal
authors.initials: T
authors.lastname: Danino
authors.forename: Dmitri
authors.initials: D
authors.lastname: Volfson
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
authors.forename: Lev
authors.initials: L
authors.lastname: Tsimring
authors.forename: Jeff
authors.initials: J
authors.lastname: Hasty
mesh_terms: D000465:Algorithms; D000818:Animals; D001808:Blood Vessels / Q000166:cytology* / Q000196:embryology; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002448:Cell Adhesion; D003198:Computer Simulation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008648:Mesoderm / Q000166:cytology*; D008954:Models, Biological; D011485:Protein Binding; D000097568:Matrix Gla Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein