The Role of Protein-protein Interactions in Mechanotransduction: Implications in Ventilator Induced Lung Injury

Critically ill patients often require mechanical ventilation to support their breathing. This is especially true for patients with Acute Respiratory Distress Syndrome, where therapeutic intervention still remains largely ineffective. A clinical study supported by the National Institutes of Health has indicated that low tidal volume ventilation is beneficial, which has established mechanical ventilation an important contributor to lung injury in these patients. Mechanical ventilation can lead to increased production of cytokines and chemokines related to inflammation and tissue damage. Further understanding of mechanotransduction may reveal targeting strategies for therapeutic intervention. It is known that cells can sense mechanical forces across the plasma membrane through a variety of mechanisms. In addition, intracellular force sensors have been proposed to play an important role in conversion of physical forces into biochemical signals through protein-protein interactions. In this chapter we reviewed this novel mechanism for mechanosensation and mechanotransduction, and proposed to inhibit Src protein tyrosine kinase activation as a potential therapy for ventilator induced lung injury.