TY - JOUR
T1 - Cell stiffness, contractile stress and the role of extracellular matrix
AU - An, Steven S.
AU - Kim, Jina
AU - Ahn, Kwangmi
AU - Trepat, Xavier
AU - Drake, Kenneth J.
AU - Kumar, Sarvesh
AU - Ling, Guoyu
AU - Purington, Carolyn
AU - Rangasamy, Tirumalai
AU - Kensler, Thomas W.
AU - Mitzner, Wayne
AU - Fredberg, Jeffrey J.
AU - Biswal, Shyam
N1 - Funding Information:
This work was supported by NIH Grants HL59682 (J.J.F.), HL33009 (J.J.F.), HL081205 (S.B.), and COPD SCCOR P50HL074945 (S.B.); by Children Asthma Center P50ES015903; by NIEHS Center grant pilot grant (S.A.); and by Faculty Research Initiative Fund from Johns Hopkins Bloomberg School of Public Health (S.A.).
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/5/15
Y1 - 2009/5/15
N2 - 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.
AB - 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.
KW - Airway hyperreactivity
KW - Airway smooth muscle
KW - Asthma
KW - ECM
KW - Nrf2
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=64749084438&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=64749084438&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.03.118
DO - 10.1016/j.bbrc.2009.03.118
M3 - Article
C2 - 19327344
AN - SCOPUS:64749084438
VL - 382
SP - 697
EP - 703
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -