Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, and National 985 Project Institute of Biorheology and Gene Regulation, Bioengineering College, Chongqing University, Chongqing, China.
Pulm Pharmacol Ther. 2009 Oct;22(5):407-16. doi: 10.1016/j.pupt.2009.04.008. Epub 2009 May 4.
Stress and strain are omnipresent in the lung due to constant lung volume fluctuation associated with respiration, and they modulate the phenotype and function of all cells residing in the airways including the airway smooth muscle (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its physical environment, and can alter its structure and/or function accordingly, resulting in either desired or undesired consequences. The forces that are either conferred to the ASM cell due to external stretching or generated inside the cell must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining appropriate levels of stress and strain within the CSK is essential for maintaining normal function. Despite the importance, the mechanisms regulating/dysregulating ASM cytoskeletal filaments in response to stress and strain remained poorly understood until only recently. For example, it is now understood that ASM length and force are dynamically regulated, and both can adapt over a wide range of length, rendering ASM one of the most malleable living tissues. The malleability reflects the CSK's dynamic mechanical properties and plasticity, both of which strongly interact with the loading on the CSK, and all together ultimately determines airway narrowing in pathology. Here we review the latest advances in our understanding of stress and strain in ASM cells, including the organization of contractile and cytoskeletal filaments, range and adaptation of functional length, structural and functional changes of the cell in response to mechanical perturbation, ASM tone as a mediator of strain-induced responses, and the novel glassy dynamic behaviors of the CSK in relation to asthma pathophysiology.
由于与呼吸相关的肺容量波动，肺中始终存在压力和应变，它们调节所有存在于气道中的细胞的表型和功能，包括气道平滑肌（ASM）细胞。有充分的证据表明，ASM 细胞对其物理环境非常敏感，可以相应地改变其结构和/或功能，从而产生期望或不期望的后果。由于外部拉伸而赋予 ASM 细胞的力或在细胞内产生的力必须在细胞骨架（CSK）内承受和传递。因此，在 CSK 内保持适当的压力和应变水平对于维持正常功能至关重要。尽管很重要，但直到最近，调节/失调 ASM 细胞骨架丝对压力和应变的反应的机制仍知之甚少。例如，现在已经了解到 ASM 的长度和力是动态调节的，两者都可以在很大的长度范围内适应，使 ASM 成为最具可塑性的活组织之一。这种可变性反映了 CSK 的动态力学特性和可塑性，两者都与 CSK 上的负载强烈相互作用，最终共同决定了病理中的气道狭窄。在这里，我们回顾了我们对 ASM 细胞中压力和应变的最新理解，包括收缩和细胞骨架丝的组织、功能长度的范围和适应性、细胞对机械扰动的结构和功能变化、ASM 张力作为应变诱导反应的介质，以及 CSK 与哮喘病理生理学相关的玻璃态动态行为。
