Mechanical tugging force regulates the size of cell-cell junctions

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Actomyosin contractility influences tissue organization via mechanical forces at cell-matrix and cell-cell contacts.
• Increased mechanical load at cell-matrix adhesions promotes focal adhesion growth, but the effect of force on cell-cell adhesion size is unknown.

Purpose of the Study:

• To investigate the force-dependent regulation of adherens junctions (AJ).
• To quantitatively measure cell-cell tugging forces and AJ size.

Main Methods:

• Utilized microfabricated force sensors to measure cell-cell tugging forces and AJ size.
• Manipulated myosin activity and Rac1 signaling.
• Applied direct mechanical tugging forces.

Main Results:

• AJ size dynamically changed with endothelial cell-cell tugging forces, increasing with myosin activation and decreasing with inhibition.
• Myosin-dependent regulation of AJs was coordinated with Rac1 signaling.
• Vascular permeability agents' effects on junctional stability were modulated by Rac1 and myosin pathways.
• Direct mechanical tugging force, independent of myosin activity, induced AJ growth.

Conclusions:

• Adherens junction size is directly modulated by mechanical tugging forces.
• The coordinated regulation of mechanical forces and cell-cell adhesion is vital for multicellular integrity.
• New methods are needed to study tugging forces in cellular contexts.