Ephrin‐A1 regulates cell dynamics through molecular activation, mechanical tension, and morphology (1180.13)

Abstract

Ephrins, the Eph family of receptor tyrosine kinases and their ligands, have been shown to be key players in guiding cell migration, polarization, and cell‐matrix and cell‐cell adhesions. Specifically, the ligand Ephrin‐A1 has been shown to regulate cell motility and morphology through the activation of EphA receptors, which signal to PI3K pathway to induce cell contraction. We performed live cell experiments on mouse embryonic fibroblasts (MEFs) to study the interrelations of molecular activation of myosin light‐chain kinase (MLCK) as determined by fluorescence resonance energy transfer (FRET), mechanical tension as measured by using novel 3D intracellular force microscopy (3D IFM), and cell morphology in response to Ephrin‐A1. The results demonstrate positive correlations among the elevation of MLCK, an increase in intracellular mechanical tension, and a reduction of cell area, which indicates an augmentation of contraction. These effects of Ephrin‐A1 were absent in MEFs with PI3K subunit p85b knockout (p85b‐/‐), indicating that p85b in PI3K plays a significant role in mediating the chemical, mechanical, and morphological effects of Ephrine‐A1. This study serves to elucidate the mechano‐chemical regulation of cell dynamics under Ephrine‐A1 guidance. Grant Funding Source: Supported by NIH HL108375 (Shu Chien), NSF: (Shaochen Chen)