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Comput Methods Biomech Biomed Engin. 2017 Jan;20(1):59-74. Epub 2016 Jun 23.

Computational model of mesenchymal migration in 3D under chemotaxis.

Author information

1
a IDMEC , Instituto Superior Técnico, Universidade de Lisboa , Lisbon , Portugal.
2
b Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering , Universidad de Zaragoza , Zaragoza , Spain.

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-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.

KEYWORDS:

3D mesenchymal migration; Gillespie’s algorithm; chemotaxis; fibroblast; phosphoinositide 3-kinase; platelet derived growth factor

PMID:
27336322
PMCID:
PMC5061084
DOI:
10.1080/10255842.2016.1198784
[Indexed for MEDLINE]
Free PMC Article

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