【作者】 王净；

【导师】 吕建仁； 徐海；

【作者基本信息】 中国石油大学 ， 化学工程与技术， 2010， 博士

【摘要】 分子自组装是当前科学研究领域的热点课题。多肽分子自组装以其丰富的自组装驱动力、新颖的聚集体形态、特殊的功能及良好的生物相容性,在纳米技术、生物材料、药物传输等方面具有广泛的应用前景。两亲性多肽具有表面活性剂两亲的特性,不同的两亲性多肽可自组装成不同的结构例如纳米纤维、纳米管、纳米囊泡。本论文设计一系列具有不同分子结构特征的两亲性多肽,通过研究其在溶液中自组装和固/液界面吸附,探讨两亲性多肽分子自组装的机理,并为两亲性多肽的应用提供理论基础。采用微波多肽固相合成方法合成具有表面活性剂特征的AmK、X6K、AnD系列两亲性多肽,并利用AFM、TEM、CD等实验手段对它们自组装行为进行表征。AmK和AnD系列两亲性多肽随着疏水尾部氨基酸残基数的增加,临界聚集浓度减小,自组装形成不同的结构。A3K自组装形成层状结构;A6K自组装形成纳米纤维结构,其直径为8.0±1.0 nm,长度超过1μm;A9K自组装形成纳米短棒结构,其直径为3.0±1.0 nm,其长度小于100 nm。两亲性多肽疏水尾部氨基酸残基数的增加和疏水尾部侧链碳原子数的不同,导致两亲性多肽的临界聚集浓度不同,分子间的相互作用力发生变化,自组装形成的纳米结构不同。A3K、A6K及A9K自组装结构不同可以应用传统表面活性剂的分子堆积理论进行解释。对AmK系列的A6K、A9K两亲性多肽的自组装动力学进行研究,A6K在溶液配制初期发生聚集,24 h形成短的纳米纤维,经过一周时间达到自组装的动态平衡,形成长度达到微米级的纳米纤维,但是纤维中仍存在断点;A9K在溶液配制1 h内即可达到自组装动态平衡,形成规则的纳米短棒结构。实验表明多肽疏水尾部的疏水相互作用力不同对其自组装的动力学过程有影响。对AmK系列的A6K、A9K两亲性多肽的在不同环境条件(pH值、温度、盐离子浓度)下自组装结构的稳定性进行了考察,A9K自组装的纳米短棒结构比A6K自组装的纳米纤维结构更稳定,疏水尾部的作用在两亲性多肽的自组装过程的稳定性中起重要作用。环境因素的改变使自组装中非共价键间的相互作用改变,两亲性多肽通过头基间的静电相互作用,疏水尾部的相互作用和分子间的氢键彼此协调,控制两亲性多肽自组装的形貌。采用SE、AFM等实验手段对AmK系列的A6K、A9K在亲水和疏水固/液界面上的吸附进行了初步研究。两亲性多肽浓度低于其临界聚集浓度(CAC)时,在亲水和疏水界面上以单体形式吸附。两亲性多肽浓度高于其CAC时,亲水界面上A6K、A9K在吸附平衡时,以在溶液中自组装形成纳米结构替换单体结构吸附在界面上;疏水界面上A6K在吸附平衡时吸附量与亲水界面上吸附量接近,推测吸附形式与亲水界面相同,而疏水界面上A9K在吸附平衡时吸附量增加,推测自组装结构受界面性质的影响,在单体吸附的结构上进一步以溶液中自组装结构吸附。疏水尾部的相互作用在两亲性多肽的自组装、自组装动力学、自组装体稳定性及界面吸附机理的过程中都起主要作用。通过两亲性多肽的自组装及其动力学和环境因素对其自组装的影响的研究,确定了该类两亲性多肽自组装的机理可以应用传统表面活性剂分子堆积理论进行解释。通过两亲性多肽在固/液界面上的吸附的研究,推测在亲水界面上,静电相互作用引发吸附,平衡时疏水相互作用起主要作用;在疏水界面上,吸附初期和平衡时疏水相互作用起主导作用。更多还原

【Abstract】 As a promising approach to fabricating novel materials and devices on the nanoscale, short peptide self-assembly has been extensively explored over the past few decades. Because of their unique features such as biocompatibility and biological modifications, peptide-based self-assembled have been found applications in the delivery of drugs, nano-technology, bio-materials. Surfactant-like peptides have been reported to self-assemble efficiently into various nanostructures, including fibers, tapes, tubes, and spheres. In this paper, we designed a series of surfactant-like peptides and studied their self-assembly. We described the dynamic self-assembly processes of peptide surfactants in aqueous solution. Our results have revealed interesting transitions in structure and dynamics of peptide molecular self-assembly. We also studied the adsorption of surfactant-like peptides at the hydrophilic and hydrophobic solid/water interface. The main conclusions are listed as follows:From a combined AFM, TEM, and CD study of a series of surfactant-like peptides AmK(m=3,6 and 9), we show that structural transitions (sheets, fibers,worm-like micelles, and short rods) can be induced by increasing the length of the hydrophobic peptide region. The trend can be interpreted using the molecular packing theory developed to describe surfactant structural transitions, but decreased CAC, and increased electrostatic interaction associated with increasing the peptide hydrophobic chain need to be taken into account appropriately. Dynamic processes of molecular self-assembly from two surfactant-like peptides A6K and A9K have been investigated. Aggregated peptide stacks were formed during the first hour of solution preparation, followed by their assembly into short nanofibrillar segments in the 24 hour period. The alignment of short nanofibers into mature long ones then occurred, with final lengths extended to several microns but with diameters remaining fixed at 5-8 nm. Even after a week, gaps or joints still remained in the mature nanofibers. In contrast, A9K self-assembled into smaller nanorods with diameters of around 3-4 nm and lengths mostly within about 100 nm. The entire self-assembling process was completed within the first hour and there were few further morphological variations afterwards.The changed of two surfactant-like peptides A6K and A9K self-assembly in different pH values, temperature and ionic strength have been studied. The structure of peptides is sensitive to the changes of pH, temperature, ionic strength. With the weak non-covalent interaction including the electrostatic interaction, intermolecular hydrogen bond and the interaction of hydrophobic tail, they could self-assembled into the nano-structure and they harmonize with each other. The interactions of hydrophobic tail play a major role in the stability of the surfactant-like peptides self-assembly process.We have focus on the interfacial adsorption of two surfactant-like peptides A6K and A9K, at the hydrophilic and hydrophobic solid/water interface. The A6K achieved its steady adsorption at the concentration of 0.5 mM while the A9K achieved its stead adsorption at the concentration of 0.05 mM on hydrophilic solid/liquid interface. At the concentration of surfactant-like peptide below the CAC, the single molecule of them is adsorbed on the interface. While above the CAC, A6K and A9K are self-assemble into nano-structure and monolayer adsorption on hydrophilic solid/liquid interface. On the hydrophobic solid/liquid interface, A6K self-assembled into nanofibers and monolayer adsorption. While the self-assembled structures of A9K changed by hydrophobic interfacial properties and double-layer adsorbed on it.The hydrophobic tail played a major role in the surfactant-like peptides self-assembly, the dynamic process of self-assembly, self-assembly stability and adsorption on different solid/liquid interface. Through the research, we illustrated the mechanism of surfactant-like peptides self-assembly and adsorption on different solid/liquid interface. Our results showed electrostatic attraction was important for initiating the adsorption and hydrophobic interaction was more dominant in determining the equilibrated amount of adsorption.更多还原