Computational model of mesenchymal migration in 3D under chemotaxis

Ribeiro, F.O. ; Gómez-Benito, M.J. (Universidad de Zaragoza) ; Folgado, J. ; Fernandes, P.R. ; García-Aznar, J.M. (Universidad de Zaragoza)

Resumen: 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-1 a 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.

Idioma: Inglés

DOI: 10.1080/10255842.2016.1198784

Año: 2017

Publicado en: Computer Methods in Biomechanics and Biomedical Engineering 20, 1 (2017), 59-74
ISSN: 1025-5842

Factor impacto JCR: 1.974 (2017)

Categ. JCR: COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS rank: 51 / 105 = 0.486 (2017) - Q2 - T2
Categ. JCR: ENGINEERING, BIOMEDICAL rank: 40 / 78 = 0.513 (2017) - Q3 - T2

Factor impacto SCIMAGO: 0.579 - Bioengineering (Q2) - Biomedical Engineering (Q2) - Medicine (miscellaneous) (Q2) - Human-Computer Interaction (Q2) - Computer Science Applications (Q2)

Financiación: info:eu-repo/grantAgreement/EUR/FP7/ERC2012-StG-306751
Financiación: info:eu-repo/grantAgreement/ES/MINECO/DPI2015-64221-C2-1-R

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)