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Force-induced growth of adhesion domains is controlled by receptor mobility

机译:力诱导的粘附域生长受受体迁移率控制

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摘要

In living cells, adhesion structures have the astonishing ability to grow and strengthen under force. Despite the rising evidence of the importance of this phenomenon, little is known about the underlying mechanism. Here, we show that force-induced adhesion-strengthening can occur purely because of the thermodynamic response to the elastic deformation of the membrane, even in the absence of the actively regulated cytoskeleton of the cell, which was hitherto deemed necessary. We impose pN-forces on two fluid membranes, locally pre-adhered by RGD-integrin binding. One of the binding partners is always mobile whereas the mobility of the other can be switched on or off. Immediate passive strengthening of adhesion structures occurs in both cases. When both binding partners are mobile, strengthening is aided by lateral movement of intact bonds as a transient response to force-induced membrane-deformation. By extending our microinterferometric technique to the suboptical regime, we show that the adhesion, as well as the resistance to force-induced de-adhesion, is greatly enhanced when both, rather than only one, of the binding partners are mobile. We formulate a theory that explains our observations by linking the macroscopic shape deformation with the microscopic formation of bonds, which further elucidates the importance of receptor mobility. We propose this fast passive response to be the first-recognition that triggers signaling events leading to mechanosensing in living cells.
机译:在活细胞中,粘附结构具有惊人的能力,可以在力的作用下生长和增强。尽管有越来越多的证据表明这种现象的重要性,但对其潜在机制知之甚少。在这里,我们表明,即使在没有主动调节的细胞骨架的情况下,也可以纯粹由于对膜的弹性变形的热力学响应而发生力诱导的粘附增强,而迄今为止,这一直被认为是必需的。我们在两个流体膜上施加pN力,这些膜被RGD-整联蛋白结合预先局部粘附。一个绑定伙伴始终是可移动的,而另一个绑定伙伴的移动性可以打开或关闭。在这两种情况下,粘合结构都会立即被动增强。当两个结合配偶体都是可移动的时,完整结合的侧向移动有助于增强作用,这是对力引起的膜变形的短暂响应。通过将我们的微干涉技术扩展到亚光学领域,我们发现当两个(而不是只有一个)结合伴侣都移动时,粘附力以及对力诱导的去粘附力的抵抗力将大大提高。我们制定了一种理论,通过将宏观形状变形与微观形成的键联系起来,从而解释了我们的观察结果,从而进一步阐明了受体迁移率的重要性。我们建议这种快速的被动响应是触发信号事件导致活细胞机械传感的第一个认识。

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