Migration of connective tissue-derived cells is mediated by ultra-low concentration gradient fields of EGF

Abstract

The directed migration of cells towards chemical stimuli incorporates simultaneous changes in both the concentration of a chemotactic agent and its concentration gradient, each of which may influence cell migratory response. In this study, we utilized a microfluidic system to examine the interactions between Epidermal Growth Factor (EGF) concentration and EGF gradient in stimulating the chemotaxis of connective-tissue derived fibroblast cells. Cells seeded within microfluidic devices were exposed to concentration gradients established by EGF concentrations that matched or exceeded those required for maximum chemotactic responses seen in transfilter migration assays. The migration of individual cells within the device was measured optically after steady-state gradients had been experimentally established. Results illustrate that motility was maximal at EGF concentration gradients between .01- and 0.1-ng/(mL.mm) for all concentrations used. In contrast, the numbers of motile cells continually increased with increasing gradient steepness for all concentrations examined. Microfluidics-based experiments exposed cells to minute changes in EGF concentration and gradient that were in line with the acute EGFR phosphorylation measured. Correlation of experimental data with established mathematical models illustrated that the fibroblasts studied exhibit an unreported chemosensitivity to minute changes in EGF concentration, similar to that reported for highly motile cells, such as macrophages. Our results demonstrate that shallow chemotactic gradients, while previously unexplored, are necessary to induce the rate of directed cellular migration and the number of motile cells in the connective tissue-derived cells examined.

Controlled microfluidics to examine growth-factor induced migration of neural progenitors in the Drosophila visual system

“…In addition, the Chemotactic index, CI, was used as the measure of directed cell migration, as defined in Eq. (2) (Kong et al, 2011): $$\text{CI}=\frac{x}{d}$$ where x is distance toward gradient and d is total accumulated distance. Values approach 1 as cells move more directly toward the gradient, are negative for cells moving away from the gradient.…”

EGF Positively Regulates the Proliferation and Migration, and Negatively Regulates the Myofibroblast Differentiation of Periodontal Ligament-Derived Endothelial Progenitor Cells through MEK/ERK- and JNK-Dependent Signals

“…However, it remains to be clarified whether the EGF/EGFR system affects the multipotency of PDL-derived undifferentiated mesenchymal cells. On the other hand, Kong et al reported that EGF positively controls migratory activity of bovine medial collateral ligament-derived fibroblasts [21]. However, it remains to be elucidated what kinds of molecular mechanisms underlie the proliferation, migration, and MF differentiation of the PDL-derived undifferentiated fibroblastic cells.…”

Role of Epidermal Growth Factor-Triggered PI3K/Akt Signaling in the Migration of Medulloblastoma-Derived Cells

“…15 Another study has demonstrated that transactivation of EGF-R via PDGFR-B activity was able to guide MB migration in vivo . 2 Further, EGF-mediated migration has been shown to be concentration gradient-dependent, as breast cancer cells, 32 fibroblast cells 21 and glioma cells 1 responded to increasing gradients of EGF via higher motility in vitro .…”