Katsuta Hiroki, Okuda Satoru, Nagayama Kazuaki, Machiyama Hiroaki, Kidoaki Satoru, Kato Masashi, Sokabe Masahiro, Miyata Takaki, Hirata Hiroaki
Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
iScience. 2023 Feb 1;26(3):106090. doi: 10.1016/j.isci.2023.106090. eCollection 2023 Mar 17.
Contractile force generated in actomyosin stress fibers (SFs) is transmitted along SFs to the extracellular matrix (ECM), which contributes to cell migration and sensing of ECM rigidity. In this study, we show that efficient force transmission along SFs relies on actin crosslinking by α-actinin. Upon reduction of α-actinin-mediated crosslinks, the myosin II activity induced flows of actin filaments and myosin II along SFs, leading to a decrease in traction force exertion to ECM. The fluidized SFs maintained their cable integrity probably through enhanced actin polymerization throughout SFs. A computational modeling analysis suggested that lowering the density of actin crosslinks caused viscous slippage of actin filaments in SFs and, thereby, dissipated myosin-generated force transmitting along SFs. As a cellular scale outcome, α-actinin depletion attenuated the ECM-rigidity-dependent difference in cell migration speed, which suggested that α-actinin-modulated SF mechanics is involved in the cellular response to ECM rigidity.
肌动球蛋白应力纤维（SFs）中产生的收缩力沿着应力纤维传递到细胞外基质（ECM），这有助于细胞迁移和对细胞外基质硬度的感知。在本研究中，我们表明，沿着应力纤维的有效力传递依赖于α-辅肌动蛋白对肌动蛋白的交联作用。当α-辅肌动蛋白介导的交联减少时，肌球蛋白II活性诱导肌动蛋白丝和肌球蛋白II沿着应力纤维流动，导致对细胞外基质施加的牵引力降低。流化的应力纤维可能通过增强整个应力纤维中的肌动蛋白聚合来维持其缆索完整性。计算模型分析表明，降低肌动蛋白交联密度会导致应力纤维中肌动蛋白丝的粘性滑动，从而耗散沿应力纤维传递的肌球蛋白产生的力。作为细胞尺度的结果，α-辅肌动蛋白的缺失减弱了细胞迁移速度中依赖于细胞外基质硬度的差异，这表明α-辅肌动蛋白调节的应力纤维力学参与了细胞对细胞外基质硬度的反应。
