Dying cells use a molecular zipper that only pops open when the cell swells up enough to pull the membrane taut.
Programmed cell death is a violent process that releases signals to the rest of the body. A protein called NINJ1 forms long filaments that act like the teeth of a zipper on the cell's outer layer. These filaments do not actually rupture the cell until internal pressure causes the membrane to stretch and thin. Once the tension reaches a critical point, the zipper opens and the cell bursts to release its contents. This mechanical trigger explains why some cells die quietly while others explode and cause massive inflammation.
Membrane Tension Drives Opening of NINJ1 Lesions in Dying Cells
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Abstract Ninjurin-1 (NINJ1) executes cell lysis by polymerizing into filaments, yet how these form membrane lesions is unknown. Integrating cell-based assays with molecular dynamics simulations, we demonstrate that NINJ1-driven membrane rupture starts with the lateral association of NINJ1 dimers into double filaments. Subsequently, swelling of necrotic cells increases plasma membrane tension, leading to separation of the filament interface and NINJ1 lesion opening. Inhibiting cell swelling preve