Targeting cytoskeletal biomechanics to modulate airway smooth muscle contraction in asthma

To contract, to deform, and remodel, the airway smooth muscle cell relies on dynamic changes in the structure of its mechanical force-bearing cytoskeleton. These alternate between a "fluid-like" (relaxed) state characterized by weak contractile protein-protein interactions within the cytoskeletal apparatus and a "solid-like" (contractile) state promoted by strong and highly organized molecular interactions. In this review, we discuss the roles for actin, myosin, factors promoting actin polymerization and depolymerization, adhesome complexes, and cell-cell junctions in these dynamic processes. We describe the relationship between these cytoskeletal factors, extracellular matrix components of bronchial tissue, and mechanical stretch and other changes within the airway wall in the context of the physical mechanisms of cytoskeletal fluidization-resolidification. We also highlight studies that emphasize the distinct processes of cell shortening and force transmission in airway smooth muscle and previously unrecognized roles for actin in cytoskeletal dynamics. Finally, we discuss the implications of these discoveries for understanding and treating airway obstruction in asthma.