PMID- 23266714 OWN - NLM STAT- MEDLINE DCOM- 20131021 LR - 20130412 IS - 1095-8541 (Electronic) IS - 0022-5193 (Linking) VI - 326 DP - 2013 Jun 7 TI - Cells as state machines: cell behavior patterns arise during capillary formation as a function of BDNF and VEGF. PG - 43-57 LID - S0022-5193(12)00619-4 [pii] LID - 10.1016/j.jtbi.2012.11.030 [doi] AB - 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. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Long, Byron L AU - Long BL AD - Department of Bioengineering, Rice University, 6100 Main St., Houston, TX 77005, USA. bl6@rice.edu FAU - Rekhi, Rahul AU - Rekhi R FAU - Abrego, Amada AU - Abrego A FAU - Jung, Jiwon AU - Jung J FAU - Qutub, Amina A AU - Qutub AA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20121222 PL - England TA - J Theor Biol JT - Journal of theoretical biology JID - 0376342 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Capillaries/drug effects/physiology MH - Cell Communication/drug effects MH - Cell Proliferation/drug effects MH - Cell Shape/drug effects/physiology MH - Cells, Cultured MH - *Computational Biology/methods MH - Endothelium, Vascular/drug effects/physiology MH - Human Umbilical Vein Endothelial Cells/cytology/*drug effects/*physiology MH - Humans MH - *Models, Biological MH - Neovascularization, Physiologic/drug effects MH - Spheroids, Cellular/drug effects/metabolism/physiology MH - Vascular Endothelial Growth Factor A/*pharmacology EDAT- 2012/12/26 06:00 MHDA- 2013/10/22 06:00 CRDT- 2012/12/26 06:00 PHST- 2012/04/20 00:00 [received] PHST- 2012/10/17 00:00 [revised] PHST- 2012/11/28 00:00 [accepted] PHST- 2012/12/26 06:00 [entrez] PHST- 2012/12/26 06:00 [pubmed] PHST- 2013/10/22 06:00 [medline] AID - S0022-5193(12)00619-4 [pii] AID - 10.1016/j.jtbi.2012.11.030 [doi] PST - ppublish SO - J Theor Biol. 2013 Jun 7;326:43-57. doi: 10.1016/j.jtbi.2012.11.030. Epub 2012 Dec 22.