Notch signaling and taxis mechanisms regulate early stage angiogenesis: A mathematical and computational model

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dc.contributor.author Vega Martínez, Rocío
dc.contributor.author Carretero Cerrajero, Manuel
dc.contributor.author Travasso, Rui D.M.
dc.contributor.author López Bonilla, Luis Francisco
dc.date.accessioned 2020-12-17T15:29:20Z
dc.date.available 2020-12-17T15:29:20Z
dc.date.issued 2020-01-01
dc.identifier.bibliographicCitation Vega R, Carretero M, Travasso RDM, Bonilla LL (2020) Notch signaling and taxis mechanisms regulate early stage angiogenesis: A mathematical and computational model. PLoS Comput Biol 16(1): e1006919
dc.identifier.issn 1553-734X
dc.identifier.uri http://hdl.handle.net/10016/31634
dc.description.abstract During angiogenesis, new blood vessels sprout and grow from existing ones. This processplays a crucial role in organ development and repair, in wound healing and in numerouspathological processes such as cancer progression or diabetes. Here, we present a mathematical model of early stage angiogenesis that permits exploration of the relative importanceof mechanical, chemical and cellular cues. Endothelial cells proliferate and move over anextracellular matrix by following external gradients of Vessel Endothelial Growth Factor,adhesion and stiffness, which are incorporated to a Cellular Potts model with a finite elementdescription of elasticity. The dynamics of Notch signaling involving Delta-4 and Jagged-1ligands determines tip cell selection and vessel branching. Through their production rates,competing Jagged-Notch and Delta-Notch dynamics determine the influence of lateral inhibition and lateral induction on the selection of cellular phenotypes, branching of blood vessels, anastomosis (fusion of blood vessels) and angiogenesis velocity. Anastomosis may befavored or impeded depending on the mechanical configuration of strain vectors in the ECMnear tip cells. Numerical simulations demonstrate that increasing Jagged production resultsin pathological vasculatures with thinner and more abundant vessels, which can be compensated by augmenting the production of Delta ligands.
dc.description.sponsorship This work has been supported by the FEDER/Ministerio de Ciencia, Innovacion y Universidades -- Agencia Estatal de Investigacion grant MTM2017-84446-C2-2-R (RV, MC and LLB), by the Ministerio de Ciencia, Innovacion y Universidades Salvador de Madariaga grant PRX18/00166 (LLB), by FEDER funds through the Operational Program Competitiveness Factors - COMPETE and by national funds by FCT - Foundation for Science and Technology under the strategic project UID/FIS/04564/2016 and under POCI-01-0145-FEDER-031743 -- PTDC/BIA-CEL/31743/2017 (RDMT), and by the FCT Researcher Program (RDMT)
dc.language.iso eng
dc.publisher Plos
dc.rights © 2020 Vega et al.
dc.rights Atribución 3.0 España
dc.rights.uri http://creativecommons.org/licenses/by/3.0/es/
dc.title Notch signaling and taxis mechanisms regulate early stage angiogenesis: A mathematical and computational model
dc.type article
dc.subject.eciencia Matemáticas
dc.identifier.doi https://doi.org/10.1371/journal.pcbi.1006919
dc.rights.accessRights openAccess
dc.relation.projectID Gobierno de España. MTM2017-84446-C2-2-R
dc.type.version publishedVersion
dc.identifier.publicationfirstpage 1
dc.identifier.publicationissue 1(e1006919)
dc.identifier.publicationlastpage 31
dc.identifier.publicationtitle PLoS Computational Biology
dc.identifier.publicationvolume 16
dc.identifier.uxxi AR/0000026346
dc.contributor.funder Ministerio de Ciencia, Innovación y Universidades (España)
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