Published ahead of print on February 16, 2006, doi:10.1165/rcmb.2005-0453OC Am. J. Respir. Cell Mol. Biol., Volume 35, Number 1, July 2006, 55-64 A more recent version of this article appeared on July 1, 2006
Submitted on December 10, 2005 Do Biophysical Properties of the Airway Smooth Muscle in Culture Predict Airway Hyperresponsiveness?Steven S An1*,1 Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA; Division of Physiology, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 Department of Physics, Erlangen University, Erlangen, Germany, 3 Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA * To whom correspondence should be addressed. E-mail: san{at}hsph.harvard.edu.
Airway hyperresponsiveness (AHR) 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 hypo-responsive Lewis rat versus the relatively hyper-responsive Fisher rat. We focused upon the ability of the cytoskeleton (CSK) of the ASM cell to stiffen, to generate contractile forces, and to remodel. To measure cell stiffness we used magnetic twisting cytometry, to measure contractile forces we used traction microscopy, and to measure remodeling dynamics we quantified spontaneous nano-scale 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. Taken together, 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.
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