Feeling the hidden mechanical forces in lipid bilayer is an original sense
Feeling the hidden mechanical forces in lipid bilayer is an original sense
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DOI：
10.1073/pnas.1313364111
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发表时间：
2014-06-03
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;Loukin, Stephen H.;Kung, Ching
生命的起源需要封闭一个隔间来储存物质、能量和信息。包膜必须包含两路通路，例如益生元脂肪酸，以分隔两个水结构域。自组装的脂质双分子层具有一系列特性，包括其具有化学或物理延展性的强各向异性内力。增加双层拉伸可以改变嵌入蛋白质上的力向量，从而影响构象变化。25年前，当拉伸打开纯化的大肠杆菌MscL通道重构成人工双层结构时，证明了脂质力原理。最近，两种脊椎动物机械敏感的K+通道（TREK1和TRAAK）严格地概括了这种简化的练习。膜拉伸也被认为可以激活各种电压、配体或Ca2+门控通道。仔细的分析表明，标准电压门控通道Kv实际上对非常小的张力也非常敏感。在一个意想不到的情况下，果蝇眼睛中典型的瞬时受体电位通道，长期以来被认为是通过配体结合打开的，显然是由于PIP2水解诱导的双层应变变化而被膜力打开的。脂质作为一种亲密的介质，既通过物理作用又通过化学作用来控制膜蛋白。这一原理并不令人惊讶，因为它与水在可溶性蛋白质的结构和功能中所起的重要作用相似。今天，明显或隐蔽的机械力控制着细胞的生物过程并产生感觉。在起源上，双分子层对渗透力的反应可能是处理反复无常的原始海洋的第一个感官。
Life's origin entails enclosing a compartment to hoard material, energy, and information. The envelope necessarily comprises amphipaths, such as prebiotic fatty acids, to partition the two aqueous domains. The self-assembled lipid bilayer comes with a set of properties including its strong anisotropic internal forces that are chemically or physically malleable. Added bilayer stretch can alter force vectors on embedded proteins to effect conformational change. The force-from-lipid principle was demonstrated 25 y ago when stretches opened purified Escherichia coli MscL channels reconstituted into artificial bilayers. This reductionistic exercise has rigorously been recapitulated recently with two vertebrate mechanosensitive K+ channels (TREK1 and TRAAK). Membrane stretches have also been known to activate various voltage-, ligand-, or Ca2+-gated channels. Careful analyses showed that Kv, the canonical voltage-gated channel, is in fact exquisitely sensitive even to very small tension. In an unexpected context, the canonical transient-receptor-potential channels in the Drosophila eye, long presumed to open by ligand binding, is apparently opened by membrane force due to PIP2 hydrolysis-induced changes in bilayer strain. Being the intimate medium, lipids govern membrane proteins by physics as well as chemistry. This principle should not be a surprise because it parallels water's paramount role in the structure and function of soluble proteins. Today, overt or covert mechanical forces govern cell biological processes and produce sensations. At the genesis, a bilayer's response to osmotic force is likely among the first senses to deal with the capricious primordial sea.