NINJ1 regulates plasma membrane fragility under mechanical strain.

Area of Science:

• Cell Biology
• Biophysics
• Membrane Biology

Background:

• Plasma membrane integrity is essential for cell function.
• Mechanical forces can damage the plasma membrane.
• The role of specific molecules in regulating mechanical strain-induced membrane damage is largely unknown.

Purpose of the Study:

• To identify proteins that regulate plasma membrane integrity under mechanical strain.
• To investigate the role of NINJ1 in mechanical-strain-induced plasma membrane rupture (PMR).

Main Methods:

• Development of a 384-well cellular-stretch system for precise strain application.
• High-throughput screening of 10,843 small interfering RNAs (siRNAs) targeting 2,726 multipass transmembrane proteins.
• Analysis of strain-induced membrane permeability changes.

Main Results:

• NINJ1 was identified as a top hit regulating strain-induced membrane permeability.
• NINJ1 is a critical regulator of mechanical-strain-induced plasma membrane rupture (PMR) independently of cell death pathways.
• NINJ1 levels inversely correlate with the force required for membrane rupture.
• NINJ1 alone is insufficient for full membrane rupture in pyroptosis; additional force is needed.

Conclusions:

• NINJ1 is a key determinant of plasma membrane biomechanical properties.
• NINJ1 expression and external forces fine-tune PMR in different mechanical microenvironments.