Airway smooth muscle and bronchospasm: fluctuating, fluidizing, freezing.
We review here four recent findings that have altered in a fundamental way our understanding of airways smooth muscle (ASM), its dynamic responses to physiological loading, and their dominant mechanical role in bronchospasm. These findings highlight ASM remodeling processes that are innately out-of-equilibrium and dynamic, and bring to the forefront a striking intersection between topics in condensed matter physics and ASM cytoskeletal biology. By doing so, they place in a new light the role of enhanced ASM mass in airway hyper-responsiveness as well as in the failure of a deep inspiration to relax the asthmatic airway. These findings have established that (i) ASM length is equilibrated dynamically, not statically; (ii) ASM dynamics closely resemble physical features exhibited by so-called soft glassy materials; (iii) static force-length relationships fail to describe dynamically contracted ASM states; (iv) stretch fluidizes the ASM cytoskeleton. Taken together, these observations suggest that at the origin of the bronchodilatory effect of a deep inspiration, and its failure in asthma, may lie glassy dynamics of the ASM cell.
Program in Molecular and Integrative Physiological Sciences, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, United States.
Ramaswamy
R
Krishnan
Xavier
X
Trepat
Trang T B
TT
Nguyen
Guillaume
G
Lenormand
Madavi
M
Oliver
Jeffrey J
JJ
Fredberg
D000818:Animals; D001986:Bronchial Spasm / Q000473:pathology* / Q000503:physiopathology; D003599:Cytoskeleton / Q000502:physiology; D005615:Freezing; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology*; D017711:Nonlinear Dynamics; D015656:Respiratory Mechanics; D012137:Respiratory System / Q000166:cytology*