Probing Endothelial Cell Mechanics Through Connexin 43 Disruption

Area of Science:

• Endothelial cell biology
• Biophysics
• Cellular mechanics

Background:

• Endothelial cells generate and transmit intercellular stresses via cell-cell junctions.
• While adherens and tight junctions are implicated, the role of gap junctions remains unclear.
• Connexin 43 (Cx43) is a key gap junction protein in endothelial cells.

Purpose of the Study:

• To investigate the relationship between Cx43 and endothelial cell biomechanics.
• To determine the impact of Cx43 disruption on intercellular stresses and cell mechanics.

Main Methods:

• Human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations of 2,5-dihydroxychalcone (chalcone), a Cx43 inhibitor.
• Traction force microscopy and monolayer stress microscopy were used to measure cell-substrate tractions and cell-cell intercellular stresses.
• Cellular velocities and strain energies were also quantified.

Main Results:

• Low chalcone concentration increased normal intercellular stresses by 17%, while high concentration decreased them by 55%.
• Shear stresses decreased by 16% (low) and 66% (high) chalcone.
• Cellular tractions, velocities, and strain energies significantly decreased with increasing chalcone concentration.

Conclusions:

• Cx43 plays a crucial role in maintaining endothelial cell biomechanics.
• Disruption of Cx43 alters intercellular stress transmission and cellular mechanical properties.
• These findings elucidate the contribution of Cx43 to endothelial cell function.