Amyloid Inspired Self-Assembled Peptide Nanofibers
Amyloid Inspired Self-Assembled Peptide Nanofibers
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DOI：
10.1021/bm301141h
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发表时间：
2012-10-01
影响因子：
6.2
通讯作者：
Guler, Mustafa O.
中科院分区：
文献类型：
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作者：
Cinar, Goksu;Ceylan, Hakan;Guler, Mustafa O.
淀粉样肽是许多退行性疾病以及维持细胞代谢的重要成分。它们独特的稳定结构为开发新材料提供了新的见解。设计受生物启发的自组装肽是产生新型分层纳米结构的必要条件。在这里，我们提出了带相反电荷的淀粉样蛋白激发肽（AIPs），在pH为7时，由于非共价相互作用而在水中混合后迅速自组装成纳米纤维。用振荡流变学方法分析了自组装AIP纳米纤维形成的凝胶的力学性能。AIP凝胶表现出较强的机械特性，优于先前报道的合成短肽自组装形成的凝胶。对带相反电荷的混合AIP分子（AIP-1 + 2）组成的凝胶的流变学研究表明，与通过pH变化中和净电荷形成的单个肽网络（AIP-1和AIP-2）相比，前者具有更好的机械稳定性。利用原子力显微镜（AFM）对AIP混合纳米纤维和电荷中和的AIP-1、AIP-2纳米纤维的粘附性能和弹性性能进行了分析。自组装的AIP-1 + 2、AIP-1和AIP-2纳米纤维的纳米力学表征也证实了宏观流变学结果，AIP混合纳米纤维的机械稳定性高于分别在酸性和碱性pH下自组装的AIP-1和AIP-2纳米纤维。通过考虑氨基酸残基之间潜在的非共价相互作用和可能的聚集形式，分子动力学模拟支持了实验结果。此外，将HUVEC细胞培养在pH为7的AIP混合纳米纤维上，观察纳米纤维体系的生物相容性和模拟胶原支架性能。在生理条件下完成了AIP纳米纤维网络中两性离子染料（罗丹明B）的封装，以证明该网络可以用于包含可溶性因子作为细胞培养研究的支架。
Amyloid peptides are important components in many degenerative diseases as well as in maintaining cellular metabolism. Their unique stable structure provides new insights in developing new materials. Designing bioinspired self-assembling peptides is essential to generate new forms of hierarchical nanostructures. Here we present oppositely charged amyloid inspired peptides (AIPs), which rapidly self-assemble into nanofibers at pH 7 upon mixing in water caused by noncovalent interactions. Mechanical properties of the gels formed by self-assembled AIP nanofibers were analyzed with oscillatory rheology. AIP gels exhibited strong mechanical characteristics superior to gels formed by self-assembly of previously reported synthetic short peptides. Rheological studies of gels composed of oppositely charged mixed AIP molecules (AIP-1 + 2) revealed superior mechanical stability compared to individual peptide networks (AIP-1 and AIP-2) formed by neutralization of net charges through pH change. Adhesion and elasticity properties of AIP mixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers were analyzed by high resolution force distance mapping using atomic force microscopy (AFM). Nanomechanical characterization of self-assembled AIP-1 + 2, AIP-1, and AIP-2 nanofibers also confirmed macroscopic rheology results, and mechanical stability of AIP mixed nanofibers was higher compared to individual AIP-1 and AIP-2 nanofibers self-assembled at acidic and basic pH, respectively. Experimental results were supported with molecular dynamics simulations by considering potential noncovalent interactions between the amino acid residues and possible aggregate forms. In addition, HUVEC cells were cultured on AIP mixed nanofibers at pH 7 and biocompatibility and collagen mimetic scaffold properties of the nanofibrous system were observed. Encapsulation of a zwitterionic dye (rhodamine B) within AIP nanofiber network was accomplished at physiological conditions to demonstrate that this network can be utilized for inclusion of soluble factors as a scaffold for cell culture studies.