Biophysical basis for airway hyperresponsivenessThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

Abstract

Airway hyperresponsiveness is the excessive narrowing of the airway lumen caused by stimuli that would cause little or no narrowing in the normal individual. It is one of the cardinal features of asthma, but its mechanisms remain unexplained. In asthma, the key end-effector of acute airway narrowing is contraction of the airway smooth muscle cell that is driven by myosin motors exerting their mechanical effects within an integrated cytoskeletal scaffolding. In just the past few years, however, our understanding of the rules that govern muscle biophysics has dramatically changed, as has their classical relationship to airway mechanics. It has become well established, for example, that muscle length is equilibrated dynamically rather than statically, and that in a dynamic setting nonclassical features of muscle biophysics come to the forefront, including unanticipated interactions between the muscle and its time-varying load, as well as the ability of the muscle cell to adapt (remodel) its internal microstructure rapidly in response to its ever-changing mechanical environment. Here, we consider some of these emerging concepts and, in particular, focus on structural remodeling of the airway smooth muscle cell as it relates to excessive airway narrowing in asthma.

Computational and experimental study of the mechanics of embryonic wound healing

“…Hence, we interpret $F_0^{f*}$ as the result of a rapid contraction of the initially unloaded fiber (time constant τ un ≪ τ f ) that slows (τ un → τ f ) as tension increases, with the observed prestretch $F_0^{f*}={false(G^{f}false)}^{-1}$ resulting from the contribution of many such fibers. This Hill-like behavior is consistent with some recent models for stress fibers (Deshpande et al, 2007; Stachowiak and O’Shaughnessy, 2008), and an ability of actomyosin fibers to rapidly contract by large amounts has been observed in smooth muscle cells (An and Fredberg, 2007). …”

“…Both the speed and magnitude of cell contraction $false(G_1^c=0.55false)$ are in line with observations for smooth muscle cells (An and Fredberg, 2007). The rate of fiber formation τ ϕ (3 min) is consistent with our observed time rate of fiber formation (see Fig.…”

“…The stress concentrations predicted by our model, particularly around elliptical wounds, are of a magnitude consistent with fiber stress exerted by smooth muscle cells (An and Fredberg, 2007). Viscoelastic effects, not incorporated in the model, are likely to reduce the peak stress considerably.…”

“…4 and Sec. 7.2.1), and the fiber contraction rate τ f (20 min) is consistent with actomyosin fiber dynamics continuing over tens of minutes following a stimulus (An and Fredberg, 2007; Brock et al, 1996). Embryonic tissues can shorten by 70% or more within a relatively short time period (Varner and Taber, 2012b), supporting the value $G_1^f=0.15$.…”

Nogo-B regulates migration and contraction of airway smooth muscle cells by decreasing ARPC 2/3 and increasing MYL-9 expression

“…It is believed that abnormalities in proliferation, apoptosis, migration, secretion, and contraction of smooth muscle cells (SMCs) all play roles in airway smooth muscle remodeling, and contribute to airway hyperresponsiveness [1,2]. …”