title: Cells as state machines: cell behavior patterns arise during capillary formation as a function of BDNF and VEGF.
abstract: Cell behavior patterns that lead to distinct tissue or capillary phenotypes are difficult to identify using existing approaches. We present a strategy to characterize the form, frequency, magnitude and sequence of human endothelial cell activity when stimulated by vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). We introduce a "Rules-as-Agents" method for rapid comparison of cell behavior hypotheses to in vitro angiogenesis experiments. Endothelial cells are represented as machines that transition between finite behavior states, and their properties are explored by a search algorithm. We rank and quantify differences between competing hypotheses about cell behavior during the formation of unique capillary phenotypes. Results show the interaction of tip and stalk endothelial cells, and predict how migration, proliferation, branching, and elongation integrate to form capillary structures within a 3D matrix in the presence of varying VEGF and BDNF concentrations. This work offers the ability to understand - and ultimately control - human cell behavior at the microvasculature level.
authors.affiliation: Department of Bioengineering, Rice University, 6100 Main St., Houston, TX 77005, USA. bl6@rice.edu
authors.forename: Byron L
authors.initials: BL
authors.lastname: Long
authors.forename: Rahul
authors.initials: R
authors.lastname: Rekhi
authors.forename: Amada
authors.initials: A
authors.lastname: Abrego
authors.forename: Jiwon
authors.initials: J
authors.lastname: Jung
authors.forename: Amina A
authors.initials: AA
authors.lastname: Qutub
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A