Contributions of the active and passive components of the cytoskeletal prestress to stiffening of airway smooth muscle cells

Abstract—Airway smoothmuscle cells exhibit stiffening during contractile activation. This stiffening may be interpreted as a result of the stabilizing influence of the mechanical prestress stored within the cytoskeleton (CSK). However, in vivo, airway smoothmuscle cells contract while simultaneously experiencing breathing-induced stretching. Excessive stretching of cells could cause actin–myosin crosslinks, and possibly other cytoskeletal filaments, to break, thereby leading to dissipation of the prestress and inhibition of further cell stiffening. The aim of this study is to investigate the stiffening behavior of individual human airway smooth muscle (HASM) cells exposed to a combination of substrate stretching, contractile activation and relaxation. We treated cultured HASM cells with either contractile (histamine) or relaxing (DBcAMP)pharmacological agonists and used magnetic cytometry technique to investigat