Stiffened lipid platforms at molecular force foci
Stiffened lipid platforms at molecular force foci
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DOI：
10.1073/pnas.1302018110
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发表时间：
2013-03-26
影响因子：
11.1
通讯作者：
Kung, Ching
中科院分区：
文献类型：
--
作者：
Anishkin, Andriy;Kung, Ching
机械力是如何被感知的，在很大程度上仍然是个谜。原核生物和几种真核生物通道的门控力被发现来自脂质膜。我们对动物细胞的研究发现，膜力焦点都有胆固醇聚集蛋白，并被胆固醇强化。这一结果在脊椎动物听觉的静纤毛尖端的明显力传感器和秀丽隐杆线虫和哺乳动物神经元的触觉感受器中是显而易见的。对于特化程度较低的细胞，钙粘蛋白维持相邻细胞之间的力，整合素维持细胞与基质之间的力。这些张力载体也通过并结合到富含胆固醇的平台，然后通过其他蛋白质锚定到细胞骨架。胆固醇与鞘磷脂和专门的蛋白质结合，在双层中形成更有序的结构。这样的加强平台可以抑制机械噪声、重定向、重缩放和限制力。我们推测这些平台可能是动态的。所施加的力可允许无序相脂质进入较薄的移动的邻域中的平台分级通道开口。该平台还可以含有封闭机械敏感通道的专门的蛋白质/脂质亚结构域，以在局部张力下打开。这样的动态阶段可以机械地操作结构上不同的通道或酶，而不必将它们直接连接到钙粘蛋白、整联蛋白或其他蛋白质系链。
How mechanical forces are sensed remains largely mysterious. The forces that gate prokaryotic and several eukaryotic channels were found to come from the lipid membrane. Our survey of animal cells found that membrane force foci all have cholesterol-gathering proteins and are reinforced with cholesterol. This result is evident in overt force sensors at the tips of stereocilia for vertebrate hearing and the touch receptor of Caenorhabditis elegans and mammalian neurons. For less specialized cells, cadherins sustain the force between neighboring cells and integrins between cells and matrix. These tension bearers also pass through and bind to a cholesterol-enriched platform before anchoring to cytoskeleton through other proteins. Cholesterol, in alliance with sphingomyelin and specialized proteins, enforces a more ordered structure in the bilayer. Such a stiffened platform can suppress mechanical noise, redirect, rescale, and confine force. We speculate that such platforms may be dynamic. The applied force may allow disordered-phase lipids to enter the platform-staging channel opening in the thinner mobile neighborhood. The platform may also contain specialized protein/lipid subdomains enclosing mechanosensitive channels to open with localized tension. Such a dynamic stage can mechanically operate structurally disparate channels or enzymes without having to tie them directly to cadherin, integrin, or other protein tethers.