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Published ahead of print on February 16, 2006, doi:10.1165/rcmb.2005-0453OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 35, pp. 55-64, 2006
© 2006 American Thoracic Society
DOI: 10.1165/rcmb.2005-0453OC

Do Biophysical Properties of the Airway Smooth Muscle in Culture Predict Airway Hyperresponsiveness?

Steven S. An, Ben Fabry, Xavier Trepat, Ning Wang and Jeffrey J. Fredberg

Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts; Division of Physiology, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Physics, Erlangen University, Erlangen, Germany

Correspondence and requests for reprints should be addressed to Steven S. An, Ph.D., Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205. E-mail: san{at}jhsph.edu

Airway hyperresponsiveness is a cardinal feature of asthma but remains largely unexplained. In asthma, the key end-effector of acute airway narrowing is the airway smooth muscle (ASM) cell. Here we report novel biophysical properties of the ASM cell isolated from the relatively hyporesponsive Lewis rat versus the relatively hyperresponsive Fisher rat. We focused upon the ability of the cytoskeleton (CSK) of the ASM cell to stiffen, to generate contractile forces, and to remodel. We used optical magnetic twisting cytometry to measure cell stiffness and traction microscopy to measure contractile forces. To measure remodeling dynamics, we quantified spontaneous nanoscale motions of a microbead tightly anchored to the CSK. In response to a panel of contractile and relaxing agonists, Fisher ASM cells showed greater stiffening, bigger contractile forces, and faster CSK remodeling; they also exhibited higher effective temperature of the CSK matrix. These physical differences measured at the level of the single cell in vitro were consistent with strain-related differences in airway responsiveness in vivo. As such, comprehensive biophysical characterizations of CSK dynamics at the level of the cell in culture may provide novel perspectives on the ASM and its contributions to the excessive airway narrowing in asthma.

Key Words: airway hyperresponsiveness • airway smooth muscle • cytoskeleton dynamics • inbred strains • remodeling




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