Nuclear envelope rupture initiation in confined migration: A geometric-kinetic framework.

Area of Science:

• Cell biology
• Biophysics
• Mechanobiology

Background:

• Nuclear envelope rupture during confined cell migration is variable.
• Pore diameter alone is insufficient to predict rupture.
• Understanding rupture mechanics is crucial for various physiological and pathological processes.

Purpose of the Study:

• To propose a novel geometric-kinetic framework to predict nuclear envelope rupture risk.
• To integrate diverse confinement events onto a unified operating-point map.
• To identify key cellular components involved in modulating rupture mechanics.

Main Methods:

• Development of a geometric-kinetic framework.
• Identification of measurable coordinates for geometric stress focusing and nuclear remodeling.
• Framing LINC complexes and cytoskeletal assemblies as force-routing modules.

Main Results:

• Rupture risk is organized along coupled axes of geometric stress and rate-limited remodeling.
• A shared operating-point map can classify diverse confinement events.
• LINC complexes and cytoskeletal assemblies can modulate rupture by altering loading, buffering, and kinematics.

Conclusions:

• The proposed framework provides a unified approach to understanding nuclear envelope rupture.
• Separating rupture initiation from nuclear damage is essential.
• The framework enables hypothesis generation for cancer invasion, immune trafficking, and fibrotic remodeling.