Membrane permeability during pressure XXXX formation: A computational model of dynamic competition between cytoskeletal damage and repair.

@entity1 @entity63 @entity39 @entity1066 @entity460 @entity5632
UNASSIGNED: Pressure @entity1066 are debilitating wounds that arise frequently in @entity1 who have lost mobility. Mechanical stress, oxidative stress and @entity63 -reperfusion injury are potential sources of damage during pressure @entity1066 formation, but cross-talk between these sources has rarely been investigated. In vitro experiments with mechanically-induced cell damage previously demonstrated that non-lethal amounts of static cell deformation could induce myoblast membrane permeabilization. Permeabilization, in turn, has the potential to induce oxidative stress via leakage of @entity460 , @entity5632 or alarmins. In this work, we constructed a hypothetical causal network of cellular-scale effects resulting from deformation and permeabilization, and we investigated the theoretical sensitivity of cell death toward various parameters and pathways of the model. Simulations showed that the survival/death outcome was particularly sensitive to the speed of membrane repair. The outcome was also sensitive to whether oxidative stress could decrease the speed of membrane repair. Finally, using the assumption that apoptosis and @entity39 would have opposite effects on membrane leakage in dying cells, we showed that promoting apoptosis might under certain conditions have the paradoxical effect of decreasing, rather than increasing, total cell death. Our work illustrates that apoptosis may have hidden benefits at preventing spatial spread of death. More broadly, our work shows the importance of membrane repair dynamics and highlights the need for experiments to measure the effects of @entity63 , apoptosis induction, and other co-occurring sources of cell stress toward the speed of membrane repair.
