Thermo- and pH-Responsive Fibrillization of Squid Suckerin A1H1 Peptide
Thermo- and pH-Responsive Fibrillization of Squid Suckerin A1H1 Peptide
复制标题
鱿鱼 Suckerin A1H1 肽的温度和 pH 响应性纤维化
DOI：
10.1039/c9nr09271d
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发表时间：
2020
期刊：
影响因子：
6.7
通讯作者：
Feng Ding
中科院分区：
文献类型：
--
作者：
Yunxiang Sun;Feng Ding
刺激响应型智能材料在纳米技术、传感和生物医学等领域有着广泛的应用前景。鱿鱼环齿中发现的Suckerin家族蛋白代表了一类基于肽的智能材料，其自组装具有优异的热塑性和pH依赖性。与嵌段共聚物类似，吸盘蛋白由两个重复序列基序组成，其中M1基序富含丙氨酸和组氨酸残基，M2富含甘氨酸。对suckerin组装体的实验研究表明，M1区主要在由M2模块组成的无定形基质中形成纳米限制的β-片层，稳定这些富含β的纳米组装体。含组氨酸的M1模块被认为是统治的pH值和温度敏感性的吸盘组装。为了更好地理解吸盘蛋白组件在分子水平上的刺激响应特性，我们系统地研究了A1 H1肽-一个代表性的M1序列-在不同温度和pH条件下的自组装动力学与原子离散分子动力学模拟。我们对20种A1 H1肽的模拟表明，在转变温度Tagg以下，它们可以通过β-折叠的初级和次级成核以及随后的通过伸长和凝固的聚集生长，从分离的单体容易地自组装成定义良好的β-折叠纳米结构。有趣的是，预形成的A1 H1 β-折叠纳米结构的解离特征在于高于Tagg的熔融温度Tm，表现出热滞后，这是具有高能量势垒的一级相变的特征。在酸性环境中，所有组氨酸残基都被质子化，A1 H1 β-折叠纳米组装体的稳定性降低，并且富含β的组装体在显著低于中性溶液的温度下容易解离成非结构化单体。计算推导的pH和温度依赖性A1 H1自组装的分子机制将有助于理解大吸盘蛋白家族的超分子组装结构和功能，并有助于未来基于肽的刺激响应智能材料的设计。
Stimuli-responsive smart materials have attracted considerable attention with numerous applications in nanotechnology, sensing, and biomedicine. Suckerin family proteins found in squid ring teeth represent such a class of peptide-based smart materials with their self-assemblies featuring excellent thermo-plasticity and pH-dependence. Similar to block copolymers, suckerin proteins are comprised of two repeating sequence motifs, where M1 motifs are abundant in alanine and histidine residues and M2 are rich in glycine. Experimental studies of suckerin assemblies suggested that M1 regions mainly formed nano-confined β-sheets within an amorphous matrix made of M2 modules stabilizing these β-rich nano-assemblies. The histidine-containing M1 modules are believed to govern the pH- and temperature-sensitive properties of suckerin assemblies. To better understand the stimuli-responsive properties of suckerin assemblies at the molecular level, we systematically studied the self-assembly dynamics of A1H1 peptides – a representative M1 sequence – at different temperatures and pH conditions with atomistic discrete molecular dynamic simulations. Our simulations with twenty A1H1 peptides demonstrated that below the transition temperature Tagg, they could readily self-assemble from isolated monomers into well-defined β-sheet nanostructures by both primary and secondary nucleation of β-sheets and subsequent aggregation growth via elongation and coagulation. Interestingly, the dissociation of pre-formed A1H1 β-sheet nanostructures featured a melting temperature Tm higher than Tagg, exhibiting the thermal hysteresis that is characteristic of first-order phase transitions with high energy barriers. In acidic environments where all histidine residues were protonated, the stability of the A1H1 β-sheet nano-assemblies was reduced and the β-rich assemblies easily dissociated into unstructured monomers at significantly lower temperatures than in the neutral solution. The computationally derived molecular mechanisms for pH- and temperature-dependent A1H1 self-assembly will help to understand the supramolecular assembly structures and functions of the large suckerin family and aid in the future design of peptide-based stimuli-responsive smart materials.