EGFR and HER2 activate rigidity sensing only on rigid matrices.

Area of Science:

• Cell Biology
• Mechanobiology
• Molecular Biology

Background:

• Epidermal growth factor receptor (EGFR) is known to interact with integrins during cell motility.
• The role of EGFR in mechanosensing processes, such as cell spreading and motility, remains largely unexplored.

Purpose of the Study:

• To investigate the role of EGFR and HER2 in cell mechanosensing, specifically rigidity sensing.
• To elucidate the mechanisms by which EGFR and HER2 contribute to cell spreading and contractions on substrates of varying stiffness.

Main Methods:

• Utilized two different cell lines to study EGFR and HER2 activity.
• Measured cell spreading and contractions on rigid and soft substrates under serum- and EGF-free conditions.
• Investigated the role of Src family kinases (SFK) and myosin-II in EGFR/HER2-mediated mechanosensing.

Main Results:

• EGFR or HER2 activity increased cell spreading and rigidity-sensing contractions on rigid substrates, but not soft ones.
• These contractions peaked early and diminished over time, with EGF addition restoring them.
• EGFR and HER2 were activated by SFK phosphorylation, and their activity was linked to nascent adhesions under tension.
• EGFR inhibition or stimulation had no effect on cell motility on soft surfaces.

Conclusions:

• EGFR and HER2 catalyze rigidity sensing by associating with nascent adhesions under SFK-dependent tension.
• EGFR and HER2 play a significant role in mechanosensing and cell behavior, particularly in the absence of EGF.
• These findings have broad implications for understanding EGFR and HER2 roles in normal and cancerous growth.