How do injured cells communicate with the surviving cell monolayer?

Area of Science:

• Cell Biology
• Wound Healing
• Cell Signaling

Background:

• Mechanical scratching of cell monolayers releases contact inhibition, prompting cell movement and proliferation.
• The response of surviving cells to wounding is debated: passive space availability versus active stimulation by injured cells.

Purpose of the Study:

• To investigate whether surviving cells respond passively to space or are actively stimulated by signals from injured cells.
• To monitor intracellular free calcium ([Ca2+]i) dynamics following mechanical injury in cell monolayers.

Main Methods:

• Scratching confluent monolayers of bovine pulmonary endothelial cells and mouse mammary epithelial cells.
• Monitoring intracellular free calcium ([Ca2+]i) using live-cell imaging.
• Manipulating extracellular calcium levels and intercellular/extracellular communication pathways.

Main Results:

• A transient elevation of [Ca2+]i was observed in surviving cells within seconds of wounding.
• The [Ca2+]i elevation propagated as a wave through the monolayer, with constant velocity but decreasing amplitude.
• Calcium influx contributed to the [Ca2+]i elevation, and mechanical wounds stimulated communication via chemical diffusion and cell-cell junctions.

Conclusions:

• Mechanical injury actively stimulates surviving cells through long-distance, [Ca2+]i-dependent communication.
• Two primary communication mechanisms were identified: diffusion of chemical signals from injured cells and transmission through cell-cell junctions.
• These findings highlight a direct chemical stimulus from mechanical injury to adjacent, undamaged cells.