Long-range stress transmission guides endothelial gap formation.

Area of Science:

• Cell biology
• Biophysics
• Mechanobiology

Background:

• Endothelial gap formation is traditionally attributed to local tractions exceeding junctional stresses.
• Understanding the physical mechanisms governing endothelial permeability is crucial for various physiological and pathological processes.

Purpose of the Study:

• To investigate the relationship between local cellular tractions, intercellular stresses, and paracellular gap formation.
• To elucidate the physical principles underlying endothelial gap formation and its impact on endothelial permeability.

Main Methods:

• Mapping of cellular tractions and intercellular stresses in response to agonist stimulation.
• Quantification of paracellular gap growth.
• Development of a minimal physical model of the endothelial cell layer.

Main Results:

• Contrary to prevailing theories, local tensile stresses showed little correlation with gap formation.
• Intercellular stresses formed distinct multi-cellular domains with defects in stress alignment.
• Paracellular gaps preferentially emerged at stress alignment defects, not at predicted stress hotspots.

Conclusions:

• Endothelial gap formation is governed by non-local, cooperative stress reorganization across the cell collective, rather than local stress imbalances.
• A new physical picture emerges, viewing the cell layer as a jammed assembly exhibiting plastic rearrangements.
• This finding redefines our understanding of endothelial permeability regulation.