title: Computational model of mesenchymal migration in 3D under chemotaxis.
abstract: Cell chemotaxis is an important characteristic of cellular migration, which takes part in crucial aspects of life and development. In this work, we propose a novel in silico model of mesenchymal 3D migration with competing protrusions under a chemotactic gradient. Based on recent experimental observations, we identify three main stages that can regulate mesenchymal chemotaxis: chemosensing, dendritic protrusion dynamics and cell-matrix interactions. Therefore, each of these features is considered as a different module of the main regulatory computational algorithm. The numerical model was particularized for the case of fibroblast chemotaxis under a PDGF-bb gradient. Fibroblasts migration was simulated embedded in two different 3D matrices - collagen and fibrin - and under several PDGF-bb concentrations. Validation of the model results was provided through qualitative and quantitative comparison with in vitro studies. Our numerical predictions of cell trajectories and speeds were within the measured in vitro ranges in both collagen and fibrin matrices. Although in fibrin, the migration speed of fibroblasts is very low, because fibrin is a stiffer and more entangling matrix. Testing PDGF-bb concentrations, we noticed that an increment of this factor produces a speed increment. At 1 ng mL-1a speed peak is reached after which the migration speed diminishes again. Moreover, we observed that fibrin exerts a dampening behavior on migration, significantly affecting the migration efficiency.
authors.affiliation: a IDMEC , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.|b Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering , Universidad de Zaragoza , Zaragoza , Spain.
authors.forename: F O
authors.initials: FO
authors.lastname: Ribeiro
authors.affiliation: b Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering , Universidad de Zaragoza , Zaragoza , Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gómez-Benito
authors.affiliation: a IDMEC , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Folgado
authors.affiliation: a IDMEC , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
authors.forename: P R
authors.initials: PR
authors.lastname: Fernandes
authors.affiliation: b Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering , Universidad de Zaragoza , Zaragoza , Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: García-Aznar
mesh_terms: D000077214:Becaplermin; D002450:Cell Communication; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D003198:Computer Simulation; D005337:Fibrin / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D008962:Models, Theoretical; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D015203:Reproducibility of Results
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D005337:Fibrin; D003094:Collagen
keywords: 3D mesenchymal migration; Gillespie’s algorithm; chemotaxis; fibroblast; phosphoinositide 3-kinase; platelet derived growth factor