Division of Bioengineering, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka, 560-8531, Japan.
Japan Society for the Promotion of Science, Tokyo, Japan.
Biomech Model Mechanobiol. 2021 Feb;20(1):155-166. doi: 10.1007/s10237-020-01375-8. Epub 2020 Aug 10.
Actin stress fibers (SFs), a contractile apparatus in nonmuscle cells, possess a contractile unit that is apparently similar to the sarcomere of myofibrils in muscles. The function of SFs has thus often been addressed based on well-characterized properties of muscles. However, unlike the fixed number of myosin molecules in myofibrils, the number of nonmuscle myosin II (NMII) within the contractile sarcomeric unit in SFs is quite low and variable for some reason. Here we address what factors may determine the specific number of NMII in SFs. We suggest with a theoretical model that the number lies just in between the function of SFs for bearing cellular tension under static conditions and for promptly disintegrating upon forced cell shortening. We monitored shortening-induced disintegration of SFs in human osteosarcoma U2OS cells expressing mutants of myosin regulatory light chain that virtually regulates the interaction of NMII with actin filaments, and the behaviors observed were indeed consistent with the theoretical consequences. This situation-specific nature of SFs may allow nonmuscle cells to respond adaptively to mechanical stress to circumvent activation of pro-inflammatory signals as previously indicated, i.e., a behavior distinct from that of muscles that are basically specialized for exhibiting contractile activity.
肌动蛋白应力纤维(SFs)是一种非肌肉细胞中的收缩装置,具有一种收缩单位,该单位显然类似于肌肉肌原纤维中的肌节。因此,SFs 的功能通常基于肌肉的特征性质来解决。然而,与肌原纤维中固定数量的肌球蛋白分子不同,SFs 中的收缩性肌节单元内的非肌肉肌球蛋白 II(NMII)数量由于某种原因相当低且可变。在这里,我们探讨了哪些因素可能决定 SFs 中的 NMII 的特定数量。我们提出了一个理论模型,表明该数量恰好介于 SFs 在静态条件下承受细胞张力的功能和在强制细胞缩短时迅速解体之间。我们监测了表达肌球蛋白调节轻链突变体的人骨肉瘤 U2OS 细胞中缩短诱导的 SFs 解体,这些突变体实际上调节了 NMII 与肌动蛋白丝的相互作用,观察到的行为确实与理论后果一致。SFs 的这种特定于情境的性质可能允许非肌肉细胞适应机械应激,以避免先前表明的促炎信号的激活,即与专门用于表现收缩活动的肌肉不同的行为。