title: Cell stiffness, contractile stress and the role of extracellular matrix.
abstract: Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. san@jhsph.edu
authors.forename: Steven S
authors.initials: SS
authors.lastname: An
authors.forename: Jina
authors.initials: J
authors.lastname: Kim
authors.forename: Kwangmi
authors.initials: K
authors.lastname: Ahn
authors.forename: Xavier
authors.initials: X
authors.lastname: Trepat
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Drake
authors.forename: Sarvesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Guoyu
authors.initials: G
authors.lastname: Ling
authors.forename: Carolyn
authors.initials: C
authors.lastname: Purington
authors.forename: Tirumalai
authors.initials: T
authors.lastname: Rangasamy
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
authors.forename: Shyam
authors.initials: S
authors.lastname: Biswal