Epithelial Wound Healing Coordinates Distinct Actin Network Architectures to Conserve Mechanical Work and Balance Power

TL;DR

This study reveals how epithelial cells coordinate different actin network architectures during wound healing to optimize mechanical work and wound closure rate, while conserving power through regulated actin transformations and cell-substrate interactions.

Contribution

It introduces a quantitative model linking actin network dynamics, mechanical work, and power conservation in collective cell migration during wound repair.

Findings

Actin network architectures modulate mechanical work during wound healing.

Mechanical work is optimized and conserved despite architectural differences.

Transformation between actin states limits the rate of mechanical work exerted.

Abstract

How cells with diverse morphologies and cytoskeletal architectures modulate their mechanical behaviors to drive robust collective motion within tissues is poorly understood. During wound repair within epithelial monolayers in vitro, cells coordinate the assembly of branched and bundled actin networks to regulate the total mechanical work produced by collective cell motion. Using traction force microscopy, we show that the balance of actin network architectures optimizes the wound closure rate and the magnitude of the mechanical work. These values are constrained by the effective power exerted by the monolayer, which is conserved and independent of actin architectures. Using a cell-based physical model, we show that the rate at which mechanical work is done by the monolayer is limited by the transformation between actin network architectures and differential regulation of cell-substrate friction. These results and our proposed molecular mechanisms provide a robust quantitative model for how cells collectively coordinate their non-equilibrium behaviors to dynamically regulate tissue-scale mechanical output.