HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/2/C440    most recent 00374.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (34) Citing Articles via Google Scholar Google Scholar Articles by Deng, L. Articles by Maksym, G. N. Search for Related Content PubMed PubMed Citation Articles by Deng, L. Articles by Maksym, G. N.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Localized mechanical stress induces time-dependent actin cytoskeletal remodeling and stiffening in cultured airway smooth muscle cells

¹School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, Canada B3H 3J5; ²Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; and ³Pediatrics Department, Case Western Reserve University, Cleveland, Ohio 44106

Submitted 2 September 2003 ; accepted in final form 2 April 2004

Mechanical stress (MS) causes cytoskeletal (CSK) and phenotypic changes in cells. Such changes in airway smooth muscle (ASM) cells might contribute to the pathophysiology of asthma. We have shown that periodic mechanical strain applied to cultured ASM cells alters the structure and expression of CSK proteins and increases cell stiffness and contractility (Smith PG, Moreno R, and Ikebe M. Am J Physiol Lung Cell Mol Physiol 272: L20–L27, 1997; and Smith PG, Deng L, Fredberg JJ, and Maksym GN. Am J Physiol Lung Cell Mol Physiol 285: L456–L463, 2003). However, the mechanically induced CSK changes, altered cell function, and their time courses are not well understood. Here we applied MS to the CSK by magnetically oscillating ferrimagnetic beads bound to the CSK. We quantified CSK remodeling by measuring actin accumulation at the sites of applied MS using fluorescence microscopy. We also measured CSK stiffness using optical magnetic twisting cytometry. We found that, during MS of up to 120 min, the percentage of beads associated with actin structures increased with time. At 60 min, 68.1 ± 1.6% of the beads were associated with actin structures compared with only 6.7 ± 2.8% before MS and 38.4 ± 5.5% in time-matched controls (P < 0.05). Similarly, CSK stiffness increased more than twofold in response to the MS compared with time-matched controls. These changes were more pronounced than observed with contractile stimulation by 80 mM KCl or 10^–4 M acetylcholine. Together, these findings imply that MS is a potent stimulus to enhance stiffness and contractility of ASM cells through CSK remodeling, which may have important implications in airway narrowing and dilation in asthma.

mechanical stress; actin cytoskeleton; stiffness; airway smooth muscle cell; optical magnetic twisting cytometry; airway constriction and dilation; asthma

This article has been cited by other articles:

				N. J. Fairbank, S. C. Connolly, J. D. MacKinnon, K. Wehry, L. Deng, and G. N. Maksym Airway smooth muscle cell tone amplifies contractile function in the presence of chronic cyclic strain Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L479 - L488. [Abstract] [Full Text] [PDF]

				S. J. Gunst and W. Zhang Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction Am J Physiol Cell Physiol, September 1, 2008; 295(3): C576 - C587. [Abstract] [Full Text] [PDF]

				D. D. Tang and Y. Anfinogenova Physiologic Properties and Regulation of the Actin Cytoskeleton in Vascular Smooth Muscle Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2008; 13(2): 130 - 140. [Abstract] [PDF]

				S. Ito, H. Kume, K. Naruse, M. Kondo, N. Takeda, S. Iwata, Y. Hasegawa, and M. Sokabe A Novel Ca2+ Influx Pathway Activated by Mechanical Stretch in Human Airway Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., April 1, 2008; 38(4): 407 - 413. [Abstract] [Full Text] [PDF]

				W. Zhang and S. J. Gunst Interactions of Airway Smooth Muscle Cells with Their Tissue Matrix: Implications for Contraction Proceedings of the ATS, January 1, 2008; 5(1): 32 - 39. [Abstract] [Full Text] [PDF]

				S. Ito, A. Majumdar, H. Kume, K. Shimokata, K. Naruse, K. R. Lutchen, D. Stamenovic, and B. Suki Viscoelastic and dynamic nonlinear properties of airway smooth muscle tissue: roles of mechanical force and the cytoskeleton Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1227 - L1237. [Abstract] [Full Text] [PDF]

				R. E. Laudadio, E. J. Millet, B. Fabry, S. S. An, J. P. Butler, and J. J. Fredberg Rat airway smooth muscle cell during actin modulation: rheology and glassy dynamics Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1388 - C1395. [Abstract] [Full Text] [PDF]

				L. Deng, N. J. Fairbank, D. J. Cole, J. J. Fredberg, and G. N. Maksym Airway smooth muscle tone modulates mechanically induced cytoskeletal stiffening and remodeling J Appl Physiol, August 1, 2005; 99(2): 634 - 641. [Abstract] [Full Text] [PDF]

				A. M. Brainard, A. J. Miller, J. R. Martens, and S. K. England Maxi-K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K+ current Am J Physiol Cell Physiol, July 1, 2005; 289(1): C49 - C57. [Abstract] [Full Text] [PDF]

				M. Puig-de-Morales, E. Millet, B. Fabry, D. Navajas, N. Wang, J. P. Butler, and J. J. Fredberg Cytoskeletal mechanics in adherent human airway smooth muscle cells: probe specificity and scaling of protein-protein dynamics Am J Physiol Cell Physiol, September 1, 2004; 287(3): C643 - C654. [Abstract] [Full Text] [PDF]