Remodeling of the airway smooth muscle cell: are we built of glass?

Classical understanding of airway lumen narrowing in asthma has held that the isometric force generated by airway smooth muscle (ASM) must be at every instant in a static mechanical equilibrium with the external load against which the muscle has shortened. It has been established recently, however, that this balance of static forces does not apply in the setting of tidal loading as occurs during breathing and must give way to the broader concepts of (1). the perturbed contractile state that exists far from static equilibrium conditions and (2). mechanical plasticity of the ASM cell. Here we describe the hypothesis that the well-established static contractile state, the newly-elaborated perturbed contractile state, as well as the remarkable mechanical plasticity of the ASM cell, are all subsumed under a rubric that is at once surprising, unifying and mechanistic. The specific hypothesis suggested is that the ASM cell behaves as a glassy material [Phys. Rev. Lett. 87 (2001) 148102]. A glass is a material that has the disordered molecular state of a liquid and, at the same time, the rigidity of a solid. If the hypothesis is true, then the ability of the ASM cytoskeleton (CSK) to deform, to flow and to remodel would be determined by an effective temperature-called the noise temperature-representing the level of jostling (i.e. molecular noise or agitation) present in the intracellular microenvironment. The abilities of the CSK to deform, to flow and to reorganize represent basic biological processes that underlie a variety of higher cell functions. If supported by the data, therefore, this integrative hypothesis might have implications in medicine and biology that go beyond the immediate issues of smooth muscle shortening and its role in asthma.