Schneider Joel P, Pochan Darrin J, Ozbas Bulent, Rajagopal Karthikan, Pakstis Lisa, Kretsinger Juliana
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA.
J Am Chem Soc. 2002 Dec 18;124(50):15030-7. doi: 10.1021/ja027993g.
A general peptide design is presented that links the pH-dependent intramolecular folding of beta-hairpin peptides to their propensity to self-assemble, affording hydrogels rich in beta-sheet. Chemical responsiveness has been specifically engineered into the material by linking intramolecular folding to changes in solution pH, and mechanical responsiveness, by linking hydrogelation to self-assembly. Circular dichroic and infrared spectroscopies show that at low pH individual peptides are unstructured, affording a low-viscosity aqueous solution. Under basic conditions, intramolecular folding takes place, affording amphiphilic beta-hairpins that intermolecularly self-assemble. Rheology shows that the resulting hydrogel is rigid but is shear-thinning. However, quick mechanical strength recovery after cessation of shear is observed due to the inherent self-assembled nature of the scaffold. Characterization of the gelation process, from the molecular level up through the macroscopic properties of the material, suggests that by linking the intramolecular folding of small designed peptides to their ability to self-assemble, responsive materials can be prepared. Cryo-transmission electron and laser scanning confocal microscopies reveal a water-filled porous scaffold on both the nano- and microscale. The environmental responsiveness, morphology, and peptidic nature make this hydrogel a possible material candidate for biomedical and engineering technology.
本文提出了一种通用的肽设计方法，该方法将β-发夹肽的pH依赖性分子内折叠与其自组装倾向联系起来，从而形成富含β-折叠的水凝胶。通过将分子内折叠与溶液pH值的变化相联系，将化学响应性专门设计到材料中；通过将水凝胶化与自组装相联系，实现了机械响应性。圆二色光谱和红外光谱表明，在低pH值下，单个肽是无结构的，形成低粘度水溶液。在碱性条件下，发生分子内折叠，形成两亲性β-发夹，它们进行分子间自组装。流变学表明，所得水凝胶是刚性的，但具有剪切变稀特性。然而，由于支架固有的自组装性质，在剪切停止后观察到快速的机械强度恢复。从分子水平到材料宏观性质对凝胶化过程进行表征表明，通过将小设计肽的分子内折叠与其自组装能力联系起来，可以制备响应性材料。冷冻透射电子显微镜和激光扫描共聚焦显微镜揭示了纳米和微米尺度上充满水的多孔支架。这种水凝胶的环境响应性、形态和肽性质使其成为生物医学和工程技术中可能的材料候选者。
