Hydrogels from Designed Peptides

描述(由申请人提供)：通过多肽自组装制备水凝胶允许人们通过设计单个组成分子来定义最终的生物材料特性。化学官能度、材料形态、粘弹性和加工性可以在自组装系统的分子水平上进行设计。在这里，多肽被设计成响应外部刺激而在分子内折叠成能够自组装的β-发夹构象。折叠的发夹可以组装成稀薄但坚硬的水凝胶，在纳米到微米的尺度上显示出孔洞。触发折叠允许对材料形成进行时间和空间控制。凝胶化会被各种生理刺激所触发；例如，pH、盐、钙离子、温度和光线。化学上良性的折叠/自组装策略，以及生成的水凝胶固有的多肽性质，为成纤维细胞和成骨细胞提供了潜在的组织工程底物。通过直接观察肽结构如何影响自组装过程、材料形态、材料特性和细胞相容性，将确定导致能够支持细胞黏附和增殖的刚性、多孔性水凝胶的肽设计原则。建议的水凝胶系统的跨学科“分子到材料”设计和性能表征将通过化学/生物化学以及材料科学和工程部门之间的密切合作来完成。这项研究工作将：1.对导致水凝胶形成的折叠和自组装过程以及分子设计如何影响材料性能有一个基本的了解。2.通过设计活性分子内折叠触发器，使多肽溶液在提示下发生水凝胶作用，提高发夹水凝胶的加工性。 3.确定多肽结构和材料性质对模型成纤维细胞和成骨细胞系黏附和增殖的影响。

DESCRIPTION (provided by applicant): The preparation of hydrogels via peptide self-assembly allows one to define ultimate biomaterial properties by design of individual constituent molecules. Chemical functionality, material morphology, viscoelasticity and processibility can be designed at the molecular level of a self-assembling system. Herein, peptides are designed to intramolecularly fold in response to external stimuli into beta-hairpin conformations that are capable of self-assembling. Folded hairpins assemble into dilute but rigid hydrogels exhibiting porosity on the nano- to -microscale. Triggered folding allows temporal and spatial control of material formation. Gelation will be triggered by various physiologically relevant stimuli; e.g. pH, salt, calcium ions, temperature and light. The chemically benign folding/self-assembly strategy, and the inherent peptidic nature of the resultant hydrogels, provide a potential tissue engineering substrate for fibroblasts and osteoblasts. Peptide design principles leading to rigid, porous hydrogels capable of supporting cell adhesion and proliferation will be determined by directly observing how peptide structure affects the self-assembly process, material morphology, material properties and cytocompatibility. The interdisciplinary "molecular to materials" design and properties characterization of the proposed hydrogelation system will be accomplished via close collaboration between the chemistry/biochemistry and materials science and engineering departments. This research effort will: 1. Gain a fundamental understanding of the folding and self-assembly process leading to hydrogel formation and how molecular design affects material properties. 2. Enhance the processibility of hairpin-based hydrogels by designing active intramolecular folding triggers that allow peptide solutions to undergo hydrogelation on cue. 3. Determine how peptide structure and material properties affect the adhesion and proliferation of model fibroblast and osteoblast cell lines.