肽自组装纳米材料的研究进展

近年来,多肽分子自组装作为合成一系列新型纳米材料的有效途径受到了广泛关注和研究.通过分子自组装,多肽分子可结合成具有不同功能的蛋白质分子,从而可进一步设计成具有特殊结构和功能的纳米材料,在仿生医学、组织工程、药物缓释及生物材料表面工程等方面有着巨大的应用潜力.本文主要综述了肽自组装纳米材料的研究现状与制备方法.     

多肽自组装及其在生物医学中的应用

多肽自组装广泛存在于自然界中。自组装多肽分子成分简单,生物相容性良好,自组装过程受多方面因素的影响,在生物医学材料方面具有巨大的应用前景。介绍了多肽分子自组装技术的概念和多肽自组装过程中的影响因素(氨基酸的组成和序列、温度、pH值、离子强度、多肽浓度、超声波),综述了多肽自组装系统的种类和多肽自组装技术在创伤修复、药物释放载体以及组织工程支架方面的应用。     

界面和溶剂对多肽二苯丙氨酸自组装的影响

多肽分子自组装是生物体中广泛存在的一种现象。自组装多肽分子成分简单,生物相容性好,但是自组装过程受多方面因素的影响。本研究借助扫描电子显微镜(SEM)对多肽二苯丙氨酸在不同界面上和不同溶剂中自组装的形貌进行了表征,圆二色谱仪(CD)、傅里叶红外光谱仪(FT-IR)分别对自组装后的二级结构以及官能团的特性等进行了表征。结果表明,二苯丙氨酸在甲醇溶液中形成α-螺旋结构,在六氟异丙醇中形成β-片层结构,且界面的不同也能调控二苯丙氨酸自组装成不同的结构,对于二苯丙氨酸自组装应用的研究有了进一步的进展。     

Au(111)表面DCDPP分子π-π堆叠的自组装特性研究

为了研究存在π-π堆叠对自组装结构的调控行为,本文利用超高真空扫描隧道显微镜研究了4,6,-二氯-2,5,-联苯嘧啶(DCDPP)分子在Au(111)上的自组装行为。DCDPP分子中旋转的5-苯环使分子中间能够存在π-π相互作用。在π堆叠,氢键等多种分子相互作用的竞争下,低覆盖度时,DCDPP在Au(111)上会形成一种链状结构和一种二维有序结构。而高覆盖度下,DCDPP将通过更高密度的自组装结构来克服高覆盖度带来的应力。这种由于不同分子间作用力和覆盖度导致不同的自主装结构的研究,对于有机电子器件的制备具有指导意义。     

自组装多肽水凝胶的制备及其在细胞培养上的应用

在生命科学的研究中,多肽自组装是一个相对前沿的领域,而基于多肽的水凝胶又是一种新型的生物材料,具有易于设计合成、制备简单、生物相容性好的特点。本文从多肽分子自身组装及外源分子辅助多肽自组装两个方面系统地总结了自组装多肽水凝胶的制备方法,并对当前多肽水凝胶的应用热点做出了评述,以期对多肽水凝胶未来的研究提供参考。     

卟啉-多肽超分子组装体系的研究进展

近年来,卟啉-多肽的超分子组装体系的研究受到了国内外学者的广泛关注,已成为超分子化学、生物材料科学研究的前沿领域之一。卟啉-多肽超分子组装体系因具有结构和功能多样化以及良好的生物相容性等优点,在生物传感、药物治疗、分子识别和光电器件等方面展示出巨大的应用潜力。文章综述了卟啉和多肽超分子构筑模块的分子结构设计、组装体的形貌调控、组装体应用3个方面的主要研究进展,介绍了卟啉与多肽分子之间的主要非共价作用方式,包括分子间静电相互作用、氢键、配位键、亲水/疏水性等,分析了该领域当前研究的焦点及亟需解决的问题。     

改性还原染料分子自组装性的研究

利用偏光显微镜、摩尔电导率和紫外-可见光光谱研究了改性还原染料如还原蓝RSN、还原猩红GG和还原深蓝BO的自组装性能,考察了浓度、温度及染料混合对其分子自组装性能的影响,分析磺化还原染料分子自组装聚集体的类型及其形成机理,结果表明分子依靠芳环间π-π共轭作用、磺酸基和溶剂水之间氢键作用力,自组装为有序结构的聚集体.磺化还原蓝RSN、磺化还原深蓝BO水溶液分子自组装为H聚集体,磺化还原猩红GG形成J聚集体.分子结构和引入亲水基影响其自组装方式和类型,一定浓度下分子自组装形成溶致液晶相,正交偏振光下,织构呈丝状、条状和粒状分布,磺化还原染料混合组装的均匀性与其浓度直接相关.     

基于硅基自组装膜的分子电子器件

文章综述了以硅为基底的自组装有机单层膜在分子电子器件中的应用,重点介绍了自组装膜的电子传导性,包括各种理论模型,如隧穿效应、热电子激发、Poole-Frankel激发以及跨越传导。此外,以烷基链(σ-分子),共轭链(π-分子)体系组成的自组装膜为基础的各种分子电子器件,如二极管、共振隧穿二极管,分子记忆和分子晶体管的概念、结构及工作原理也一并被讨论。     

有机共轭自组装材料及应用

超分子化学自组装的重要研究内容是组装体的分子设计、合成及其组装过程。为了构筑和调控某些具有特殊功能的超分子自组装体,针对不同的应用要求,可引入具有独特光电性质及刚性的有机π-共轭分子作为基本组装单元,通过超分子弱相互作用组装成功能性纳米/微米材料。总结了近年来国内外有机共轭分子的自组装行为,并介绍了其在纳米/微米光波导材料、有机小分子光电器件、分子机器及超分子传感器中的相关应用。     

多环萜类化合物自组装研究及应用

多环萜类化合物因含有独特的刚性环骨架、手性结构和多修饰位点,具有优异的自组装功能。由于萜数量和环结构不同,萜类化合物具有多种自组装形态和功能,在材料领域具有广泛的应用而备受关注。结合化合物结构特点和组装原理(电荷作用、亲水疏水作用、π-π堆积、氢键、空间位阻等作用),综述了多环萜类化合物的自组装研究现状及在靶向载药、功能材料和离子识别等领域的应用。并对多环萜类化合物自组装研究进行展望,指出开展萜类衍生物自组装构效关系研究以及理论计算辅助实验进行自组装机理研究的重要意义。     

Dynamic behaviors of lipid-like self-assembling peptide A6D and A6K nanotubes

Nanoscience and nanotechnology require development of nanomaterials that are amiable for molecular design from bottom up. Molecular designer self-assembling peptides are one of such nanomaterials that will become increasingly important for the endeavor. Peptides have not only been used in all aspects of biomedical and pharmaceutical research and medical products, but also have had enormous impact in nascent field of designed biological materials. We here report the dynamic structures of lipid-like designer peptide A6D (AAAAAAD) and A6K (AAAAAAK) that undergo self-assembly into nanotubes in water and salt solution. We not only analyzed their self-assemblies using dynamic light scattering to determine the critical aggregation concentration (CAC), but also use atomic force microscope to observe their nanostructures. We also propose a simple scheme by which these lipid-like peptides self-assemble into dynamic nanostructures. Since the knowledge of CAC is important for uses of these peptides for a variety of applications, these findings may have significant implications in the study of molecular self-assembly and for a wide range of utilities of designer self-assembling peptide materials.     

Constructing biomaterials using self-assembling peptide building blocks

Molecular self-assembly is ubiquitous in nature and has recently emerged as a new bottom-up approach in constructing biomaterials. Synthetic peptides assemble through specific molecular recognition and form diverse nanostructures. The resulting versatile peptide self-assemblies may be used in a wide range of biological and medical applications. Examples of two self-assembling peptide systems are presented and techniques for self-assembly control are discussed.     

Constructing biomaterials using self-assembling peptide building blocks

Molecular self-assembly is ubiquitous in nature and has recently emerged as a new bottom-up approach in constructing biomaterials. Synthetic peptides assemble through specific molecular recognition and form diverse nanostructures. The resulting versatile peptide self-assemblies may be used in a wide range of biological and medical applications. Examples of two self-assembling peptide systems are presented and techniques for self-assembly control are discussed.     

Systematic studies of a self-assembling peptide nanofiber scaffold with other scaffolds

A designer self-assembling peptide nanofiber scaffold has been systematically studied with 10 commonly used scaffolds in a several week study using neural stem cells (NSC), a potential therapeutic source for cellular transplantations in nervous system injuries. These cells not only provide a good in vitro model for the development and regeneration of the nervous system, but may also be helpful in testing for cytotoxicity, cellular adhesion, and differentiation properties of biological and synthetic scaffolds used in medical practices. We tested the self-assembling peptide nanofiber scaffold with the most commonly used scaffolds for tissue engineering and regenerative medicine including PLLA, PLGA, PCLA, collagen I, collagen IV, and Matrigel. Additionally, each scaffold was coated with laminin in order to evaluate the utility of this surface treatment. Each scaffold was evaluated by measuring cell viability, differentiation and maturation of the differentiated stem cell progeny (i.e. progenitor cells, astrocytes, oligodendrocytes, and neurons) over 4 weeks. The optimal scaffold should show high numbers of living and differentiated cells. In addition, it was demonstrated that the laminin surface treatment is capable of improving the overall scaffold performance. The designer self-assembling peptide RADA16 nanofiber scaffold represents a new class of biologically inspired material. The well-defined molecular structure with considerable potential for further functionalization and slow drug delivery makes the designer peptide scaffolds a very attractive class of biological material for a number of applications. The peptide nanofiber scaffold is comparable with the clinically approved synthetic scaffolds. The peptide scaffolds are not only pure, but also have the potential to be further designed at the molecular level, thus they promise to be useful for cell adhesion and differentiation studies as well as for future biomedical and clinical studies.     

自组装短肽系统及其材料学应用

模仿天然蛋白质的氨基酸序列设计自组装短肽作为纳米材料近年来引起了人们极大的兴趣。本文介绍了几个发展较为成熟的自组装短肽材料以及它们在纳米医学和纳米生物技术等领域的应用,阐述了自组装短肽作为新型纳米材料的巨大潜力。     

Self-assembling peptide nanofiber hydrogels for central nervous system regeneration

Central nervous system (CNS) presents a complex regeneration problem due to the inability of central neurons to regenerate correct axonal and dendritic connections. However, recent advances in developmental neurobiology, cell signaling, cell--matrix interaction, and biomaterials technologies have forced a reconsideration of CNS regeneration potentials from the viewpoint of tissue engineering and regenerative medicine. The applications of a novel tissue regeneration-inducing biomaterial and stem cells are thought to be critical for the mission. The use of peptide nanofiber hydrogels in cell therapy and tissue engineering offers promising perspectives for CNS regeneration. Self-assembling peptide undergo a rapid transformation from liquid to gel upon addition of counterions or pH adjustment, directly integrating with the host tissue. The peptide nanofiber hydrogels have mechanical properties that closely match the native central nervous extracellular matrix, which could enhance axonal growth. Such materials can provide an optimal three dimensional microenvironment for encapsulated cells. These materials can also be tailored with bioactive motifs to modulate the wound environment and enhance regeneration. This review intends to detail the recent status of self-assembling peptide nanofiber hydrogels for CNS regeneration.     

Effect of a synthetic link N peptide nanofiber scaffold on the matrix deposition of aggrecan and type II collagen in rabbit notochordal cells

Self-assembling peptide nanofiber scaffolds have been studied extensively as biological materials for 3-dimensional cell culture and repairing tissue defects in animals. However, few studies have applied peptide nanofiber scaffolds in the tissue engineering of intervertebral discs (IVDs). In this study, a novel functionalized peptide scaffold was specifically designed for IVD tissue engineering, and notochordal cells (NCs) as an alternative cell source for IVD degeneration were selected to investigate the bioactive scaffold material. The novel RADA16-Link N self-assembling peptide scaffold material was designed by direct coupling to a bioactive motif link N. The link N nanofiber scaffold (LN-NS) material was obtained by mixing pure RADA16-I and RADA16-Link N (1:1) designer peptide solutions. Although live/dead cell assays showed that LN-NS and RADA16-I scaffold materials were both biocompatible with NCs, the LN-NS material significantly promoted NC adhesion compared with that of the pure RADA16-I SAP scaffold material. The depositions of aggrecan and type II collagen, which are significant markers for IVD cells, were remarkably increased. Furthermore, the results indicated that the link N motif, the matrix analog of the nucleus pulposus, significantly promoted the accumulation of other extracellular matrices in vitro. We conclude that the novel LN-NS material is a promising biological scaffold material, and may have a broad range of applications in IVD tissue engineering.     

Engineering the morphology of a self-assembling protein fibre

Biological assemblies provide inspiration for the development of new materials for a variety of applications. Our ability to realize this potential, however, is hampered by difficulties in producing and engineering natural biomaterials, and in designing them de novo. We previously described a self-assembling system comprising two short complementary segments of straight synthetic polypeptides (termed standards in this report). Their interaction results in the formation of long fibres--about 50 nm in diameter--that extend straight and without branching for tens to hundreds of micrometres. Our aim is to influence and, ultimately, to control fibre morphology. Here, we show that the standard peptides can be supplemented with special peptides to effect morphological changes in the fibres. Specifically, we created half-sized subunits of the standard peptides, which were combined to make nonlinear peptides. When mixed with the standard peptides, these nonlinear peptides produced kinked, waved and branched fibres. We related the numbers of these features to the special/standard ratios empirically. Furthermore, the extent and frequency of kinking was altered by changing the standard-fibre background: more kinking was observed in a background of thinner, less-stable fibres. The ability to perform such transformations holds promise for bottom-up assembly and engineering responsive biomimetic materials for applications in surface and tissue engineering.     

Design of single peptides for self-assembled conduction channels

Self-assembly of peptides provides the possibility of achieving relatively long range order on surfaces. These ordered peptides can also form channels that can be used as conduction channels. In the past, studies were focused on electron conduction through the secondary structure and amine bond of peptides and these restrict conduction of electrons over a short range (a few nanometers). In this work, we demonstrate the realization of electron conduction over a longer range of a few hundred nanometers via π-π stacking of the phenyl groups in the tyrosine residue of a single peptide. The peptide used in this work was designed with a phenyl ring for π-π stacking at one end and a carboxylic group at the other end for binding to aminopropyltriethoxysilane (APTES) treated silicon wafer. The distance between the peptides is controlled by a disulfide bond formed between neighboring cysteine residue and also by the amine groups of aminopropyltriethoxysilane. We demonstrate that the self-assembled peptide is conducting in the dry state over hundreds of nanometers, realizing the possibility of using peptide as a molecular wire.