Strange dynamics of a dynamic cytoskeleton.
A novel physical perspective of molecular interactions within the cytoskeleton of the airway smooth muscle cell may help to explain why the most efficacious of all known bronchodilatory agencies-a simple deep inspiration-becomes abrogated during the spontaneous asthma attack and leads thereby to excessive airway narrowing. This perspective invites us to think of airway smooth muscle not only biochemically as a nidus of traditional cell signaling and immune modulation or mechanically as a motor for generation of active forces but also physically as a phase of soft condensed matter that can restrict airway stretch and dilation. This is perhaps a risky path and is surely an unconventional one, but it is where the trail of evidence leads. This line of investigation is unlikely by itself to provide an asthma cure but will lead to a new conceptual framework without which novel pathways, unsuspected phase transitions, and unanticipated mechanisms of action of target molecules would almost surely remain hidden. Glassy dynamics of the cytoskeleton are likely to be important in a wide range of biological functions and disease processes, but had it not been for their preeminent role in bronchospasm, they might never have been discovered.
Nguyen
Trang T B
TT
Program in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Room 1-313, 665 Huntington Avenue, Boston, MA 02115, USA.
Fredberg
Jeffrey J
JJ
D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology / Q000503:physiopathology*; D012143:Respiratory Physiological Phenomena; D013314:Stress, Mechanical