NINJ1 regulates plasma membrane fragility under mechanical tension

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Plasma membrane integrity is essential for cell survival and function.
• Mechanical stress is known to damage cell membranes, but the molecular regulators are unclear.

Purpose of the Study:

• To identify proteins that regulate plasma membrane integrity under mechanical stress.
• To investigate the role of NINJ1 in mechanical force-induced membrane rupture.

Main Methods:

• Development of a 384-well cellular stretch system for precise mechanical strain application.
• High-throughput siRNA screening of 2,726 multi-pass transmembrane proteins.
• Assessing stretch-induced membrane permeability changes.

Main Results:

• NINJ1 was identified as a top hit regulating stretch-induced membrane permeability.
• NINJ1 is a critical regulator of mechanical force-induced plasma membrane rupture (PMR) independently of cell death pathways.
• NINJ1 expression levels inversely correlate with the membrane tension required for rupture.

Conclusions:

• NINJ1 is a bona fide determinant of membrane biomechanical properties.
• NINJ1 fine-tunes plasma membrane rupture in response to mechanical forces.
• Cellular responses to mechanical stress are modulated by NINJ1 expression and external forces.