Mechanical ventilation contributes greatly to both morbidity and mortality of the Acute Respiratory Distress Syndrome. Unlike a broken bone which can be cast, one cannot immobilize the lungs, so that even lung protective ventilator settings may not spare the injured lungs from further damage. Our group studies the determinants of cellular stress failure because it is a central driver of the lungs' innate immune response to deforming stress. We have shown that cells of lungs, which are exposed to mechanical ventilation with high volumes and trans-pulmonary pressure, experience reversible plasma membrane wounds and that cell wounding can trigger pro-inflammatory signaling cascades. We have also shown that environmental factors such as alveolar hypercapnia, hypocapnia and associated pH changes adversely influence pulmonary cell repair, and have pointed out that different biologic manifestations of deformation injury such as edema, cell wounding and the release of inflammatory mediators need not be correlated in space and time. I will show work in progress about therapies designed to protect alveolar epithelial cells from deformation injury. I will focus on osmotic stress as a lung-protective intervention. I will show that hypertonic salt and sugar solutions increase the cytoskeleton's state of polymerization, promote plasma membrane remodeling and thereby improve the ability of alveolar epithelial cells to maintain sublytic plasma membrane tension in the face of deforming stress.