Topological Adaptation of Transmembrane Domains to the Force-Modulated Lipid Bilayer Is a Basis of Sensing Mechanical Force.,Current Biology

当前位置： X-MOL 学术 › Curr. Biol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Topological Adaptation of Transmembrane Domains to the Force-Modulated Lipid Bilayer Is a Basis of Sensing Mechanical Force.
Current Biology ( IF 8.1 ) Pub Date : 2020-03-12 , DOI: 10.1016/j.cub.2020.02.028
Jiyoon Kim ₁ , Joonha Lee ₁ , Jiyoung Jang ₁ , Feng Ye ₂ , Soon Jun Hong ₃ , Brian G Petrich ₄ , Tobias S Ulmer ₅ , Chungho Kim ₁

Affiliation

Cells can sense and respond to various mechanical stimuli from their surrounding environment. One of the explanations for mechanosensitivity, a lipid-bilayer model, suggests that a stretch of the membrane induced by mechanical force alters the physical state of the lipid bilayer, driving mechanosensors to assume conformations better matched to the altered membrane. However, mechanosensors of this class are restricted to ion channels. Here, we reveal that integrin αIIbβ3, a prototypic adhesion receptor, can be activated by various mechanical stimuli including stretch, shear stress, and osmotic pressure. The force-induced integrin activation was not dependent on its known intracellular activation signaling events and was even observed in reconstituted cell-free liposomes. Instead, these mechanical stimuli were found to alter the lipid embedding of the integrin β3 transmembrane domain (TMD) and subsequently weaken the αIIb-β3 TMD interaction, which results in activation of the receptor. Moreover, artificial modulation of the membrane curvature near integrin αIIbβ3 can induce its activation in cells as well as in lipid nanodiscs, suggesting that physical deformation of the lipid bilayer, either by mechanical force or curvature, can induce integrin activation. Thus, our results establish the adhesion receptor as a bona fide mechanosensor that directly senses and responds to the force-modulated lipid environment. Furthermore, this study expands the lipid-bilayer model by suggesting that the force-induced topological change of TMDs and subsequent alteration in the TMD interactome is a molecular basis of sensing mechanical force transmitted via the lipid bilayer.

中文翻译：

跨膜结构域对力调制脂质双层的拓扑适应是感知机械力的基础。

细胞可以感知和响应来自周围环境的各种机械刺激。对机械敏感性的一种解释是脂质双层模型，它表明由机械力引起的膜的拉伸改变了脂质双层的物理状态，从而驱动机械传感器假设构象与改变的膜更好地匹配。然而，这类机械传感器仅限于离子通道。在这里，我们揭示了整合素αIIbβ3，一种原型粘附受体，可以被各种机械刺激激活，包括拉伸、剪切应力和渗透压。力诱导的整合素激活不依赖于其已知的细胞内激活信号事件，甚至在重组的无细胞脂质体中观察到。反而，发现这些机械刺激会改变整合素 β3 跨膜结构域 (TMD) 的脂质嵌入，并随后削弱 αIIb-β3 TMD 相互作用，从而导致受体激活。此外，人工调节整合素αIIbβ3附近的膜曲率可以诱导其在细胞和脂质纳米盘中的活化，这表明脂质双层的物理变形，无论是通过机械力还是曲率，都可以诱导整合素活化。因此，我们的结果将粘附受体确立为真正的机械传感器，它直接感知并响应力调制的脂质环境。此外，

更新日期：2020-03-12

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11