Fibroblast migration in 3D is controlled by haptotaxis in a non-muscle myosin II-dependent manner

Cell migration in 3D is a key process in many physiological and pathological processes. Although valuable knowledge has been accumulated through analysis of various 2D models, some of these insights are not directly applicable to migration in 3D. In this study, we have confined biomimetic hydrogels within microfluidic platforms in the presence of a chemoattractant (platelet-derived growth fac- tor-BB). We have characterized the migratory responses of human fibroblasts within them, particularly focusing on the role of non-muscle myosin II. Our results indicate a prominent role for myosin II in the integration of chemo- tactic and haptotactic migratory responses of fibroblasts in 3D confined environments

Fibroblast Migration in 3D is Controlled by Haptotaxis in a Non-muscle Myosin II-Dependent Manner

Cell migration in 3D is a key process in many physiological and pathological processes. Although valuable knowledge has been accumulated through analysis of various 2D models, some of these insights are not directly applicable to migration in 3D. In this study, we have confined biomimetic hydrogels within microfluidic platforms in the presence of a chemoattractant (platelet-derived growth factor-BB). We have characterized the migratory responses of human fibroblasts within them, particularly focusing on the role of non-muscle myosin II. Our results indicate a prominent role for myosin II in the integration of chemotactic and haptotactic migratory responses of fibroblasts in 3D confined environments.Grants: EUR/7FP/ERC-2012-StG 306751 ES/MINECO - DPI2012-38090-C03-01 ES/MINECO - SAF2011- 2495

Computational model of mesenchymal migration in 3D under chemotaxis

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

Porosity and diffusion in biological tissues. Recent advances and further perspectives

We present a review of porosity and diffusion in biological tissues from different perspectives. We first introduce the topic by illustrating experimental evidence related to diffusion in porous media and review a number of state of the art experimental techniques. We then proceed by providing a revisited derivation of the equations of poroelasticity from the microstructure (via asymptotic homogenization), which is especially aimed at giving a first insight on the topic to both students and scientists who are not familiar with the subject. Results based on this kind of models have only recently been presented in the literature and could possibly complement the experiments by getting a more thorough understanding on the complex interplay between porosity and diffusion. We investigate further the matter by exploring the role of diffusion in driving growth and stresses in the context of linear elastic modeling for tumors and cellular automata. We finally conclude the chapter by (a) discussing diffusion in nonlinear, “active” materials, i.e., those which are possibly characterized by growth and remodeling, and (b) offering an overview on cutting edge research problems on diffusion for this class of complex materials