Eukaryotic cells can undergo different forms of programmed cell death, many of which culminate in plasma membrane rupture (PMR) as the defining terminal event. PMR was long thought to be driven by osmotic pressure, until it was recently shown to be in many cases an active process, mediated by the protein ninjurin-1 (NINJ1). Here, we studied whether the newly resolved cryo-electron microscopy NINJ1 filaments are capable to cap membrane edges by multiscaling molecular dynamics simulations. Site-directed mutagenesis was employed to validate the function of the resulting supramolecular arrangement. The membrane protein NINJ1 is thus an interactive component of the eukaryotic cell membrane that functions as an in-built breaking point in response to activation of cell death.

GROMACS, 2020 and 2021