ABSTRACT
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.
Subject(s)
Cell Movement/physiology , Fibroblasts/physiology , Myosin Type II/physiology , Becaplermin , Cell Movement/drug effects , Cells, Cultured , Fibroblasts/drug effects , Humans , Hydrogels , Microfluidics , Proto-Oncogene Proteins c-sis/pharmacologyABSTRACT
Microfluidic devices allow for the production of physiologically relevant cellular microenvironments by including biomimetic hydrogels and generating controlled chemical gradients. During transport, the biomolecules interact in distinct ways with the fibrillar networks: as purely diffusive factors in the soluble fluid or bound to the matrix proteins. These two main mechanisms may regulate distinct cell responses in order to guide their directional migration: caused by the substrate-bound chemoattractant gradient (haptotaxis) or by the gradient established within the soluble fluid (chemotaxis). In this work 3D diffusion experiments, in combination with ELISA assays, are performed using microfluidic platforms in order to quantify the distribution of PDGF-BB and TGF-ß1 across collagen and fibrin gels. Furthermore, to gain a deeper understanding of the fundamental processes, the experiments are reproduced by computer simulations based on a reaction-diffusion transport model. This model yields an accurate prediction of the experimental results, confirming that diffusion and binding phenomena are established within the microdevice.
