Abstract
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. (C) 2003
Elsevier B.V. All rights reserved.
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