Nguyen Trang T B, Fredberg Jeffrey J
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.
Proc Am Thorac Soc. 2008 Jan 1;5(1):58-61. doi: 10.1513/pats.200705-055VS.
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.
气道平滑肌细胞细胞骨架内分子相互作用的一种全新物理学视角,或许有助于解释为何所有已知支气管扩张剂中最有效的一种——简单的深呼吸——在自发性哮喘发作期间会失效,进而导致气道过度狭窄。这种视角促使我们不仅从生物化学角度将气道平滑肌视为传统细胞信号传导和免疫调节的核心,或者从机械角度将其视为产生主动力的动力源,还从物理学角度将其视为一种软凝聚态物质,这种物质能够限制气道的伸展和扩张。这或许是一条充满风险的道路,肯定也是一条非传统的道路,但这是证据所指向的方向。这条研究路线本身不太可能带来哮喘的治愈方法,但将引领我们走向一个新的概念框架,没有这个框架,新的途径、未被怀疑的相变以及靶分子意想不到的作用机制几乎肯定会一直隐藏下去。细胞骨架的玻璃态动力学可能在广泛的生物学功能和疾病过程中都很重要,但如果不是因为它们在支气管痉挛中起着至关重要的作用,可能永远都不会被发现。