Acute lung injury (ALI) is a common, frequently hospital-acquired condition with a high morbidity and mortality. The stress associated with invasive mechanical ventilation represents a potentially harmful exposure, and attempts to minimize deforming stress through low tidal ventilation have proven efficacious. Lung cells are both sensors and transducers of deforming stress, and are frequently wounded in the setting of mechanical ventilation. Cell wounding may be one of the drivers of the innate immunologic and systemic inflammatory response associated with mechanical ventilation. These downstream effects of mechanotransduction have been referred to collectively as "Biotrauma". Our review will focus on cellular stress failure, that is cell wounding, and the mechanisms mediating subsequent plasma membrane repair, we hold that a better mechanistic understanding of cell plasticity, deformation associated remodeling and repair will reveal candidate approaches for lung protective interventions in mechanically ventilated patients. We will detail one such intervention, lung conditioning with hypertonic solutions as an example of ongoing research in this arena.