Overview
This lecture covers how the protein NINJ1 regulates plasma membrane fragility and rupture in cells subjected to mechanical strain, establishing its central role in membrane biomechanics.
Importance of Plasma Membrane Integrity
- Plasma membrane integrity is crucial for all cellular functions.
- Mechanical forces can cause plasma membrane damage in cells.
Experimental Approach
- Researchers developed a 384-well cellular stretch system to apply reproducible mechanical strain to cultured cells.
- A screening was performed using 10,843 siRNAs targeting 2,726 multi-pass transmembrane proteins to identify regulators of membrane permeability under strain.
Discovery and Role of NINJ1
- NINJ1 emerged as the top hit in the siRNA screen for mediating strain-induced membrane permeability.
- NINJ1 is a key regulator for plasma membrane rupture (PMR) caused by mechanical strain, independent of cell death pathways.
- The amount of NINJ1 present on the plasma membrane inversely correlates with the force required to induce membrane rupture.
Context of Pyroptosis and Mechanical Rupture
- During pyroptosis (a form of inflammatory programmed cell death), NINJ1 alone does not fully rupture the membrane; additional mechanical force is required for complete PMR.
Implications and Biological Significance
- NINJ1 is established as a determinant of membrane biomechanical properties.
- Variation in NINJ1 expression and levels of mechanical force can fine-tune plasma membrane rupture across different tissue environments.
Key Terms & Definitions
- Plasma membrane — the outer boundary of a cell that controls the movement of substances in and out.
- Mechanical strain — physical force applied to cells, causing deformation or stress.
- siRNA (small interfering RNA) — tool for silencing specific genes to study their functions.
- NINJ1 — a transmembrane protein that regulates plasma membrane rupture.
- Pyroptosis — a type of programmed cell death involving cell lysis and inflammation.
- Plasma membrane rupture (PMR) — the breaking of the plasma membrane, leading to cell contents spilling out.
Action Items / Next Steps
- Review the mechanisms of plasma membrane repair and rupture.
- Read further on NINJ1’s role in cell death pathways and tissue biomechanics.