Mechanotransduction and the extracellular matrix: Key drivers of lung pathologies and drug responsiveness

The lung is a biomechanically active organ, with multiscale mechanical forces impacting the organ, tissue and cellular responses within this microenvironment. In chronic lung diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis and others, the structure of the lung is drastically altered impeding gas exchange. These changes are, in part, reflected in alterations in the composition, amount and organization of the extracellular matrix within the different lung compartments. The transmission of mechanical forces within lung tissue are broadcast by this complex mix of extracellular matrix components, in particular the collagens, elastin and proteoglycans and the crosslinking of these components. At both a macro and a micro level, the mechanical properties of the microenvironment have a key regulatory role in ascertaining cellular responses and the function of the lung. Cells adhere to, and receive signals from, the extracellular matrix through a number of different surface receptors and complexes which are important for mechanotransduction. This review summarizes the multiscale mechanics in the lung and how the mechanical environment changes in lung disease and aging. We then examine the role of mechanotransduction in driving cell signaling events in lung diseases and finish with a future perspective of the need to consider how such forces may impact pharmacological responsiveness in lung diseases.