Mechanotransduction, the process of how cells sense and convert mechanical stimuli
into biochemical response, is crucial in the migration of leukocytes or cancer cells
through the endothelium during inflammation or metastasis. Migrating cells exert forces
on the endothelium through cell surface adhesion molecules, such as platelet endothelial
adhesion molecule PECAM-1, and this is essential for a successful transmigration.
To study PECAM-1-mediated mechanotransduction, we applied PECAM-1-antibody-coated
magnetic beads and exerted about 40 pN force on the endothelial monolayer. We show
that force increases cell–ECM adhesion in the cell center and is accompanied by the
opening of cell–cell junctions. Upon depletion of the MEK/ERK kinase, BRAF force increases
cell–ECM adhesion both at the cell periphery and in the cell center, but this does
not result in the opening of cell–cell junctions. Decreasing cell–ECM adhesion in
BRAF-depleted cells through FAK inhibition results in the remodeling of cell–cell
junctions. Force-induced increase in cell–ECM adhesion in the cell center correlates
with the activation of the transcriptional cofactor Yes-associated protein (YAP).
Furthermore, the induced activation of YAP through LATS inhibition prevents junctional
remodeling in control cells. Thus, the activation of YAP might determine the strength
of cell–cell junctions during PECAM-1-mediated mechanotransduction.
