1. EPHRIN-A1 INDUCES CELL CONTRACTION TO EXERT THREE-DIMENSIONAL TRACTION FORCE ON THE SUBSTRATE VIA A PI3K-DEPENDENT PATHWAY
Name: Min-Shu Chan
Grad Year: 2012
The Eph family of receptor tyrosine kinases and their ligands, Ephrins, have been shown to play important roles in regulating cell migration, polarization, and cell-matrix and cell-cell adhesions. Specifically, Ephrin-A1 has been shown to regulate cell contraction via activating EphA receptors that signal to the PI3K pathway. In the current study, Ephrin-A1 treatment of mouse embryonic fibroblasts (MEFs) caused the emergence of retraction fibers and cell edge retraction in the wild type, but not in those with PI3K subunit p85 knockout, suggesting that the Ephrin-A1 induction of cell contraction is p85-dependent. To quantify the forces generated in MEFs under Ephrin-A1 treatment, three-dimensional traction forces microscopy was employed to deduce the forces in cells seeded on polyacrylamide deformable substrate embedded with fluorescent beads. Three-dimensional images of the bead displacements were acquired with confocal microscopy, and the traction forces were computed in tangential and normal directions with the finite element method using MATLAB. The results demonstrated that the tangential traction force of wild-type MEFs increased after Ephrin-A1 treatment, while no significant change was observed in knockout MEFs. These findings indicate that Ephrin-A1 induces cell contraction, hence exerting forces to the substrate, via a PI3K-p85 dependent pathway.