Unraveling the molecular mechanisms of membrane rupture: Insights from all-atom simulations and theoretical modeling

Cell membrane rupture occurs universally and is long thought to be the terminal event of cell death; however, there is an inadequate understanding of the microscopic mechanisms of membrane rupture at the molecular level. In this study, we investigated the rupture mechanism of two model membranes, 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and cholesterol bilayer membranes, under surface tension by all-atom molecular simulations and theoretical modeling. Under surface tension, the tail chains of POPC molecules become disordered, leading to ductile membrane deformation, while cholesterol membranes display limited deformation before rupture. We analyzed the orientation of tail chains and the internal stresses within the membranes, revealing that the mutual attraction among different tail chains and the resulting stress peak in the tail region of the membrane play substantial roles in the membrane rupture process. Based on these physical insights, we proposed a theoretical model that incorporates an internal variable of tail chain orientation to capture the variations in strain and orientation of different membrane components under varying surface tensions. The critical rupture threshold predicted by our theoretical model aligns well with the simulation results, demonstrating a brittle to ductile transition for membranes with different cholesterol contents. Our study unravels the impact of tail chain orientation and internal stress on membrane mechanics, which deepens the understanding of the microscale mechanisms underlying membrane rupture.