Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels
Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels
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DOI：
10.1242/jcs.02760
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发表时间：
2006-02-01
影响因子：
4
通讯作者：
Ingber, DE
中科院分区：
文献类型：
--
作者：
Matthews, BD;Overby, DR;Ingber, DE
为了了解细胞如何感知和适应机械应力，我们对与细胞表面整合素受体结合的磁性微珠施加张力，并使用光学显微镜以亚微米分辨率测量磁珠位移的变化。细胞表现出四种类型的机械反应：（1）立即粘弹性反应； (2)早期自适应行为，其特征是响应振荡力的脉冲间衰减； (3) 随后具有持续（> 15 秒）静态应力的自适应单元硬化； (4) 长时间（> 1 分钟）压力下的大规模重新定位反应。重要的是，这些适应反应在生化方面有所不同。即时和早期反应受到化学消散细胞骨架预应力（等长张力）的影响，而后期的适应性反应则不受影响。与立即和早期反应的情况类似，通过干扰 Rho 信号传导抑制张力来阻止重新定位反应，但也可以通过阻断机械敏感离子通道或抑制 Src 酪氨酸激酶来阻止重新定位反应。将细胞冷却至 4 摄氏度以减缓生化重塑，从而抑制所有适应性反应。因此，细胞使用多种机制来感知和响应施加于整合素的机械应力水平的静态和动态变化。
To understand how cells sense and adapt to mechanical stress, we applied tensional forces to magnetic microbeads bound to cell-surface integrin receptors and measured changes in bead displacement with sub-micrometer resolution using optical microscopy. Cells exhibited four types of mechanical responses: (1) an immediate viscoelastic response; (2) early adaptive behavior characterized by pulse-to-pulse attenuation in response to oscillatory forces; (3) later adaptive cell stiffening with sustained (> 15 second) static stresses; and (4) a large-scale repositioning response with prolonged (> 1 minute) stress. Importantly, these adaptation responses differed biochemically. The immediate and early responses were affected by chemically dissipating cytoskeletal prestress (isometric tension), whereas the later adaptive response was not. The repositioning response was prevented by inhibiting tension through interference with Rho signaling, similar to the case of the immediate and early responses, but it was also prevented by blocking mechanosensitive ion channels or by inhibiting Src tyrosine kinases. All adaptive responses were suppressed by cooling cells to 4 degrees C to slow biochemical remodeling. Thus, cells use multiple mechanisms to sense and respond to static and dynamic changes in the level of mechanical stress applied to integrins.