Rational design of charged peptides that self-assemble into robust nanofibers as immune-functional scaffolds.
Rational design of charged peptides that self-assemble into robust nanofibers as immune-functional scaffolds.
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DOI：
10.1016/j.actbio.2017.03.041
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发表时间：
2017-06
影响因子：
9.7
通讯作者：
Woodrow KA
中科院分区：
文献类型：
--
作者：
Zhang H;Park J;Jiang Y;Woodrow KA
通过序列设计编程以形成预定义纳米结构的自组装肽可用于各种生物医学应用。然而，经典的离子自互补肽的组装体在中性pH下是不稳定的，而带电肽水凝胶具有低的机械强度。在这里，我们报告了一个自组装肽系统的合理设计与优化的电荷分布和密度的生物支架的发展。我们的设计肽采用在全pH范围（pH 0至14）内经历盐触发自组装成富含β-折叠的阳离子纳米纤维的序列模式。我们的肽在生理条件下以最低浓度形成纳米原纤维，所述最低浓度显著低于已经报道的可比较肽的自组装。我们的肽具有强大的纤维形成能力，可在生理条件下快速形成具有强大机械强度的水凝胶。此外，即使在与模型生物活性货物OVA 257 -264肽密集缀合后，也保持纤维结构。携带OVA 257 -264的纳米纤维在体外显著增强CD 8 + T细胞活化。我们的肽纤维疫苗的皮下免疫也在体内引起了稳健的CD 8 + T细胞活化和增殖。我们的自组装肽有望提供一个多功能的平台，构建不同的生物材料。
Self-assembling peptides programed by sequence design to form predefined nanostructures are useful for a variety of biomedical applications. However, assemblies of classic ionic self-complementary peptides are unstable in neutral pH, while charged peptide hydrogels have low mechanical strength. Here, we report on the rational design of a self-assembling peptide system with optimized charge distribution and density for bioscaffold development. Our designer peptides employs a sequence pattern that undergoes salt triggered self-assembly into β-sheet rich cationic nanofibers in the full pH range (pH 0 to 14). Our peptides form nanofibrils in physiological condition at a minimum concentration that is significantly lower than has been reported for self-assembly of comparable peptides. The robust fiber-forming ability of our peptides results in the rapid formation of hydrogels in physiological conditions with strong mechanical strength. Moreover, fiber structure is maintained even upon dense conjugation with a model bioactive cargo OVA257–264 peptide. Nanofibers carrying OVA257–264 significantly enhanced CD8+ T cell activation in vitro. Subcutaneous immunization of our peptide fiber vaccine also elicited robust CD8+ T cell activation and proliferation in vivo. Our self-assembling peptides are expected to provide a versatile platform to construct diverse biomaterials.
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影响因子：
15
作者：
Aggeli, A;Bell, M;Boden, N
通讯作者：
Boden, N
影响因子：
64.8
作者：
Aggeli, A;Bell, M;Radford, SE
通讯作者：
Radford, SE
影响因子：
62.1
作者：
Du X;Zhou J;Shi J;Xu B
通讯作者：
Xu B
影响因子：
6.2
作者：
Owczarz, Marta;Casalini, Tommaso;Arosio, Paolo
通讯作者：
Arosio, Paolo
影响因子：
6.2
作者：
Rajagopal, Karthikan;Lamm, Matthew S.;Schneider, Joel P.
通讯作者：
Schneider, Joel P.