Interactions of Airway Smooth Muscle Cells with Their Tissue Matrix Implications for Contraction

The ability of airway smooth muscle to alter its stiffness and contractility in response to mechanical oscillation and stretch is critically important for the regulation of normal airway responsive-ness during breathing. The properties of mechanical adaptation in airway smooth muscle are proposed to result from dynamic cyto-skeletal processes outside of the actomyosin interaction. The acto-myosin interaction and crossbridge cycling are viewed as compo-nents of a complex and integrated array of cytoskeletal events that occur during cell contraction. These events are orchestrated by macromolecular protein complexes that associatewith the cytoplas-mic domains of integrin proteins at the adhesion junctions between muscle cells and the extracellular matrix. According to this para-digm, these concerted cytoskeletal events are essential components of the process of active tensiongeneration in airway smoothmuscle, and also serve to adapt the shape and stiffness of the smoothmuscle cell to its environment. Contractile stimuli initiate actin polymeriza-tionwithin the submembranous cortex of the airway smoothmuscle cell that may serve to determine the cells shape and strengthen the membrane. The recruitment of structural proteins such as a-actinin to adhesion junctions fortifies the strength of the connections between membrane adhesion junctions and actin filaments. These processes create a strong and rigid cytoskeletal framework for the transmission of force generated by the interaction of myosin and actin filaments. This model for the regulation of airway smooth muscle function can provide novel perspectives to explain the normal physiologic behavior of the airways and pathophysiologic properties of the airways in asthma