Integration of single and multicellular wound responses

Area of Science:

• Cell biology
• Developmental biology
• Biophysics

Background:

• Wound healing in single cells and multicellular tissues are traditionally viewed as distinct processes.
• A common mechanism, the Rho GTPase-dependent purse string of actin filaments (F-actin) and myosin-2, is observed in both single-cell and epithelial wound closure.
• The integration of these distinct processes remains incompletely understood.

Purpose of the Study:

• To investigate the signaling and mechanical integration of single-cell and multicellular wound healing.
• To elucidate the role of Rho GTPase and cell-cell junctions in bridging these healing paradigms.
• To determine if calcium signaling contributes to the multicellular response.

Main Methods:

• Wounding and ablation of single cells in Xenopus embryos.
• Live imaging of Rho GTPase activation, F-actin, and myosin-2 dynamics.
• Analysis of cell-cell junctional responses to injury.
• Monitoring of intracellular free calcium levels.

Main Results:

• Wounding a single cell in Xenopus embryos triggers Rho GTPase activation at the wound and adjacent cell-cell junctions.
• F-actin and myosin-2 accumulate at junctions and the wound, forming a hybrid purse string that closes the defect.
• Ablation of cells also activates Rho GTPase and F-actin at surrounding junctions, leading to purse string closure.
• Intracellular calcium elevation, crucial for single-cell healing, is also observed at cell contacts and in neighboring cells during multicellular responses.

Conclusions:

• Single-cell and multicellular purse string wound responses are part of a continuous spectrum.
• Cell-cell junctions are key integration points, mechanically and signal-wise, between single-cell and multicellular wound repair.
• Rho GTPase and calcium signaling pathways are conserved and integrated across different scales of wound healing.