title: Smooth muscle length adaptation and actin filament length: a network model of the cytoskeletal dysregulation.
abstract: Length adaptation of the airway smooth muscle cell is attributable to cytoskeletal remodeling. It has been proposed that dysregulated actin filaments may become longer in asthma, and that such elongation would prevent a parallel-to-series transition of contractile units, thus precluding the well-known beneficial effects of deep inspirations and tidal breathing. To test the potential effect that actin filament elongation could have in overall muscle mechanics, we present an extremely simple model. The cytoskeleton is represented as a 2-D network of links (contractile filaments) connecting nodes (adhesion plaques). Such a network evolves in discrete time steps by forming and dissolving links in a stochastic fashion. Links are formed by idealized contractile units whose properties are either those from normal or elongated actin filaments. Oscillations were then imposed on the network to evaluate both the effects of breathing and length adaptation. In response to length oscillation, a network with longer actin filaments showed smaller decreases of force, smaller increases in compliance, and higher shortening velocities. Taken together, these changes correspond to a network that is refractory to the effects of breathing and therefore approximates an asthmatic scenario. Thus, an extremely simple model seems to capture some relatively complex mechanics of airway smooth muscle, supporting the idea that dysregulation of actin filament length may contribute to excessive airway narrowing.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA. silveira@usp.br
authors.forename: Paulo S P
authors.initials: PS
authors.lastname: Silveira
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000222:Adaptation, Physiological; D000818:Animals; D001696:Biomechanical Phenomena; D006801:Humans; D007537:Isometric Contraction; D008954:Models, Biological; D009130:Muscle, Smooth / Q000502:physiology*; D012119:Respiration; D012137:Respiratory System