title: A biomechanical model of agonist-initiated contraction in the asthmatic airway.
abstract: This paper presents a modelling framework in which the local stress environment of airway smooth muscle (ASM) cells may be predicted and cellular responses to local stress may be investigated. We consider an elastic axisymmetric model of a layer of connective tissue and circumferential ASM fibres embedded in parenchymal tissue and model the active contractile force generated by ASM via a stress acting along the fibres. A constitutive law is proposed that accounts for active and passive material properties as well as the proportion of muscle to connective tissue. The model predicts significantly different contractile responses depending on the proportion of muscle to connective tissue in the remodelled airway. We find that radial and hoop-stress distributions in remodelled muscle layers are highly heterogenous with distinct regions of compression and tension. Such patterns of stress are likely to have important implications, from a mechano-transduction perspective, on contractility, short-term cytoskeletal adaptation and long-term airway remodelling in asthma.
authors.affiliation: School of Mathematical Sciences, University Park, University of Nottingham, Nottingham, UK. bindi.brook@nottingham.ac.uk
authors.forename: B S
authors.initials: BS
authors.lastname: Brook
authors.forename: S E
authors.initials: SE
authors.lastname: Peel
authors.forename: I P
authors.initials: IP
authors.lastname: Hall
authors.forename: A Z
authors.initials: AZ
authors.lastname: Politi
authors.forename: J
authors.initials: J
authors.lastname: Sneyd
authors.forename: Y
authors.initials: Y
authors.lastname: Bai
authors.forename: M J
authors.initials: MJ
authors.lastname: Sanderson
authors.forename: O E
authors.initials: OE
authors.lastname: Jensen
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000473:pathology / Q000503:physiopathology*; D001696:Biomechanical Phenomena / Q000502:physiology; D003238:Connective Tissue / Q000502:physiology; D004548:Elasticity / Q000502:physiology; D066298:In Vitro Techniques; D008168:Lung / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008954:Models, Biological; D008962:Models, Theoretical; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology*; D013997:Time Factors